PL3102 Finals Revision Notes

Pre-Lecture 1: Membrane Potentials; Electrical signalling in neurons

1.1:
 Cells that compose the nervous system
 Structures that allow these cells to communicate with each other

Santiago Ramon y Cajal (1906): nervous system is composed of a number of individual cells, or
neurons, using a staining technique (stained a small proportion of random cells in brain tissue)
- Key observation: Wide variety of neuronal morphology can be observed across the nervous
system, of different types of cells encountered.

Nervous system (location) composes neurons and glia cells.

 Prevalence: Glia cells outnumber neurons by roughly 10 to 1
 Functions:
o Astrocytes: Regulation of neuron-to-neuron communication, transfer of nutrients
from blood to neurons, building myelin sheaths covering axons to increase
transmission speed of action potentials
o Microglia: Removal of pathogens and dead cell bodies from the brain
o Radial glia: Creating highways for neuron migration during development

Nervous system contains 100 billion neurons which receive and transmit information.
Found in cerebellum (70 billion), cerebral cortex (10-15 billion) and spinal cord (1 billion)

Structure of neuron
 Soma (cell body)
o Contains cell’s nucleus with its DNA (ribosomes, mitochondria etc); surface covered
with synapses
 Dendrites (dendritic tree)
o Lined with synaptic receptors to receives input from other neurons
o Dendritic spines increase surface area so more information can be received; occur at
individual synaptic contacts and specialised for synaptic connections
 Nothing more than small protrusions that come out of the main branch of the
dendrite
 In very close contact with an axonal terminal from another neuron
 Axons
o Send output of neuron to other neurons / organs / muscles; transmits action potential;
vertebrate axons covered with myelin sheath

How do neurons communicate with each other?

 Through small molecules of chemicals (neurotransmitters) that change activity of
postsynaptic neuron
 Synaptic transmission: one-way communication
o From the axon of the presynaptic neuron (releases neurotransmitters)
o To the dendrite of the postsynaptic neuron (detects neurotransmitters)
1.2:

Electricity: Flow of electric charge

 Ohm’s law: voltage (V) = current (I) * resistance (R)
o Voltage (V): difference in electrical potential energy between two points
o Current (I) / electric flow
o Resistance (R): Measure of how hard it is for charge to pass through material
 Conductance (G) : Inverse of resistance (1 / R)
o Low resistance = current flows easily = high conductance

Transmission of information by the brain

Through electrical impulses / action potentials, the movement of changes in membrane voltage down
the axon

Membrane of neuron:
 Primarily composed of hydrophobic lipids
 Oval phospholipid bilayer with water trapped inside, and water outside
 Proteins in membranes link interior and exterior of cell, for chemicals to pass through

Equilibrium potential of specific ion

 Ion: atom or molecule with an electrical charge due to loss or gain of electron(s)
 Ions present in different concentrations inside and outside of cell (eg. K+ more concentrated
inside)  concentration gradient formed
 Overall charge inside and outside cell is 0: every positive ion is balanced by a negative ion
 Membrane proteins:
o Ion channels: selectively allow passage of certain ions only (eg. K+)
 No energy needed, as long as it’s open, (K+) ions can flow down
electrochemical gradient
 Concentration (chemical) gradient – drives out K+ which is more concentrated inside cell
when gate opens.
o As K+ starts exiting, charge imbalance created inside and outside the cell, such that
the inside becomes negative while the outside becomes positive.
 Electrical gradient created - since positive ions are attracted to negative charges, K+ ions will
want to go into the cell, where it is more negative.
 These 2 opposing forces (concentration gradient pushing K+ outside; electric gradient
pushing K+ inside) eventually balance out and reach a point of equilibrium: both forces are
identical, net flow of ions is zero. Every K+ that goes out of the cell another K+ will enter the
cell: equilibrium potential for a specific ion.

Equilibrium potential (Nernst potential): membrane potential at which net flow of ions (or current)
is zero, given a specific intra- and extra-cellular concentration of ion.
*Electricity: flow of electric charge
 Equilibrium potential: membrane potential that leads to zero ionic current (equilibrium) given
a certain ionic concentration  defined by concentration gradient and ion’s charge
o Equilibrium potential of an ion changes depending on its concentration
 Inside cell: many negative charged proteins
 Outside cell: high concentration of Na+ and Cl- ions
  Resting membrane potential: membrane potential counting all ion species
o At rest, neuron not firing action potentials: Only K+ channels open; Na+ channels
closed
o At rest, overall movement: K+ out, Na+ in (membrane potential slightly more
depolarised than Nernst potential of K+)
 Electrical force driving K+ into cell (inside is negative) < electrical force
required to perfectly match chemical force driving K+ out (K+ more
concentrated inside)  K+ exits
 Still has Na+ entering cell (otherwise membrane potential = Nernst potential
of K+)  Na+ must have some conductance, driving membrane potential
slightly towards positive Nernst potential
o Resting membrane potential is close to the reversal / Nernst potential of K+, at around
negative 70mV, since highest conductance of neurons is to K+

Cell maintenance of difference in concentration of Na+ and K+ across membrane

 Cells constantly leaving K+ and Na+  over time concentration difference for them inside
and outside cell would disappear if nothing maintains gradience
 Hence cell produces transmembrane protein Na+/K+ ATPase (Na+/K+ pump)  pumps K+
in, Na+ out
 Energy (ATP) is needed as movement of both ions goes against their concentration gradients
 Results in chemical gradient of Na+ and K+ stabilising

1.3:

Nerve impulse / action potential: Rapid change in membrane voltage

- Travels down axon, from soma to axonal terminals

Initiation of action potential:

 At rest: voltage of membrane is usually around -70mV due to open K+ channels)
o Few K+ channels open
o No Na+ channels open
o Membrane potential is close to the K+ reversal potential
 Neuron begins to depolarise slowly (increase membrane potential) due to synaptic input
o If initial depolarisation crosses a certain threshold (eg. around -60mV)
 Action potential is all-or none
o Magnitude of depolarisation will always be the same, as long as the threshold is
crossed
 Membrane depolarises rapidly
o Process driven by opening of voltage-gated Na+ channels
 Much more numerous than the open K+ channels
 Voltage also opens K+ channels, but slower
 Hence huge increase of Na+ conductance compared to K+)
o Lots of Na+ enter before K+, hence membrane depolarises
o Membrane voltage gets closer to the reversal potential of Na+ (around +60mV) –
membrane brought from negative resting membrane potential towards positive
membrane potential
 o As soon as some voltage-gated Na+ channels open  drives further depolarisation 
drives opening of even more Na+ channels.
 Neuron starts repolarising rapidly (or hyperpolarisation):
o Process driven by opening of voltage-gated K+ channels in addition to always-open
K+ channels that maintain resting membrane potential (slower to open than Na+
channels) and simultaneous closure (inactivation) of voltage-gated Na+ channels
o Voltage of the membrane starts dropping quickly (back to negative potential,
approaching reversal potential of K+) after a few microseconds
 Voltage of the membrane doesn’t stop at the resting membrane potential
o Huge increase in conductance of K+ compared to Na+
o Membrane potential brought even closer to the reversal potential of K+ (around -
80mV) at negative peak of action potential
 Finally, the membrane slowly returns to its resting state of around -70mV due to the slow
closure of the voltage-gated K+ channels
o Voltage slowly increases to resting membrane potential
o After peak of action potential: 2 refractory periods

- Depolarisation: change in electric charge distribution, resulting in a less negative charge

inside cell compared to outside
- Repolarisation: Return of membrane potential to its negative value after depolarisation phase
- Hyperpolarisation: Decrease in membrane potential
- Afterhyperpolarisation: dip in cell’s membrane potential that makes it more negative than
resting potential of cell

1.4:

Action potential: dynamic change in membrane potential

Change in membrane potential propagates down the axon towards the axon terminals
Different parts of the membrane take turns to go through the voltage changes seen in an action
potential.

Propagation of action potential down axon in neuron membrane

 Due to diffusion of ions
 Close to the cell body, the action potential begins
 Na+ enters the cell through the voltage gated Na+ channels
o Higher concentration of Na+ in that segment compared to adjacent locations
o Action potential triggered by opening of these channels
o Channels open up as soon as membrane crosses voltage threshold (due to
depolarisations occurring in dendrites of neurons after receiving synaptic input)
o Enough input received  voltage of membrane around axon hillock crosses voltage
threshold  channels quickly open up
 Na+ diffuses left and right down its concentration gradient
o Na+ diffused to the right  new piece of membrane becomes depolarised
o Voltage-gated Na+ channels open in new segment
o Simultaneously, in the first segment voltage-gated K+ channels open 
repolarisation in that segment
  Neuron repolarises due to the closure of voltage-gated ion channels, which is
due to an inactivation of the channel.
 Voltage-gated Na+ channel has to have 2 open doors for Na+ to pass. One is
the regular door, and the second one is the inactivation door
 Na+ diffuses to the next segment again, depolarising it  initiates action potential in that new
segment
o Action potential does not move backwards, because the segment of membrane is very
hyperpolarized due to the open voltage-gated K+ channels
 First segment went back to resting membrane potential
o Hence action potential moves down the axon in one direction (towards the axonal
terminals).

Refractory period: period following action potential where it is impossible (initially) or harder
(later) to fire another action potential
 Absolute refractory period: period following an action potential in which the neuron cannot
fire another action potential
o Due to closed inactivation gates of voltage-gated Na+ channels
o No matter how depolarised the membrane is these inactivation gates don’t open
o No matter how much inputs neuron receives, will not fire action potential
o Only time allows these gates to open, for the initiation of a new action potential
 Relative refractory period: Period following an action potential in which it is harder (but not
impossible) to fire another action potential, compared to at rest
o Occurs after inactivation gates open
o Due to the extremely negative membrane potential during the afterhyperpolarization
 membrane more hyperpolarized at rest
o To initiate another action potential: neuron requires much more synaptic input to
depolarise it enough to reach the action potential threshold

Myelin:
 An insulating sheath around an axon
 Made up of the membranes of glia cells, that wrap around multiple axons nearby.
 Increases the speed of action potential conduction
 Formed by many layers of membrane that wrap around the axon.
 Action potential jumps from node of Ranvier to node of Ranvier until it reaches, very quickly,
the axon terminals.
o Nodes of Ranvier: holes with no myelin in between
Pre-Lecture 2:

2.1: Synaptic transmission

Components of a synapse:
 Axonal terminal from a presynaptic cell
o Located right next to postsynaptic dendritic spine
o Identify axon by synaptic vesicles (small spherical membranes filled with
neurotransmitters)
 Each synaptic vesicle has 2 or more neurotransmitters.
 Glutamatergic / GABAergic synapse means glutamate or GABA released;
doesn’t mean other neurotransmitters are not released at the same time.
 Dendritic spine of the postsynaptic cell
 Synaptic cleft: space in between the pre- and post-synaptic cell
 Glia cell: surrounding the synapse

Synaptic transmission: First step - electrical transmission down the axon leads to the release of
neurotransmitters from the presynaptic axon terminal

Neurotransmitters: Released to the synaptic cleft after an action potential reaches the presynaptic
axonal terminal

 Categorised based on molecular structure.

 Simple amino acids (structural blocks of all proteins): primary neurotransmitters in the
nervous system
o Most excitatory synapses are mediated by glutamate, while most inhibitory synapses
are mediated by GABA
 Modifications of basic amino acids: chemically modified to generate neurotransmitters
o Much less common in the brain; have very important functions.
 Neuropeptides: small sequences of amino acids.
 Much less common:
o ATP (main source of energy in body)
o Gases eg. nitride oxide

Synaptic transmission: Second step - detection of neurotransmitters by receptors in the postsynaptic

dendrite
 - May lead to a change in electrical charge (or membrane potential) in the dendrite.

Two types of membrane receptors in postsynaptic cell:

 Receptor itself is an ion channel.
o Neurotransmitter binds to receptor  changes configuration  channel opens
o Similar to voltage-gated ion channels, except instigator is when specific chemical /
neurotransmitter binds to it (rather than changes in voltage).
o Also known as ligand-gated ion channels / ionotropic receptors (exert effect directly
through the passage of ions)
 Receptor opens ion channels indirectly, through the action of intracellular processes.
o Neurotransmitter binds to receptor  evokes biochemical changes in molecules
inside the cell  molecules diffuse and open ion channels in the vicinity.
o Also known as G-protein-coupled receptor: key protein that interacts with these
receptors is called G-protein.
o Also called metabotropic receptors (exert their effect through metabolic pathways)

Receptors in membrane of postsynaptic cells bind to specific neurotransmitters  ion channels open
 cell depolarises
- Initial depolarisation (just before the voltage reaches the threshold of action potential) is due
to synaptic input.
- Synapse activated in a dendrite  ion channels that open up depolarize the dendrite.
- Voltage change in a dendrite propagates down towards the cell body (like how voltage
propagates along an axon during an action potential)
- Could take hundreds, or even thousands of simultaneous active synapses to be able to reach
the threshold for action potential.

Synaptic transmission: Third step - leftover neurotransmitters are

Destroyed in the synaptic cleft
Reabsorbed (reuptake) by the presynaptic neuron or the glia surrounding the synapse

Drug action:
 Amphetamines (eg. Adderall used to treat ADHD) and cocaine increase the release of
dopamine.
 Amphetamines, cocaine and Methylphenidate (Ritalin, also used to treat ADHD) block the
reuptake of dopamine in dopaminergic neurons
o Reuptake of neurotransmitters from the synaptic cleft occurs after release
 Increase of dopamine release + decrease in reuptake  a lot more dopamine in the synaptic
cleft, lasts for a lot longer.

2.2: Neuronal computations

Temporal and spatial summation of presynaptic inputs in neurons to activate postsynaptic neuron:
 Postsynaptic neuron has 3 inputs (other neurons that is synapsing onto it)
o Presynaptic neuron: sends information
o Postsynaptic neuron: receives information
 Spatial summation: postsynaptic neuron is summing inputs in different locations (different
dendrites)
 o All 3 neurons are active simultaneously  postsynaptic neuron crosses the threshold
and fires and action potential.
 Temporal summation: postsynaptic neuron summing inputs from the same source over time to
cross the threshold
o Only one of the input neurons active; other 2 silent
o Postsynaptic neuron doesn’t cross the threshold; also remains silent.
o One active neuron starts firing at a higher rate  postsynaptic neuron will fire an
action potential.

Spatial summation:
 Postsynaptic neuron computes the order in which inputs arrive
o Eg. Neuron in the retina encodes direction of movement of a light in space.
 Inputs arrive in different locations of the dendrite
o Eg. Closer to / further from the soma
 First input arrives (neuron 1 releases neurotransmitter)  received by the postsynaptic neuron
receptors  open up ion channels which depolarise that segment of membrane
o Small depolarisation occurs at synapse
o Depolarisation in locations adjacent to the synapse of smaller magnitude (since ions
diffuse to the sides)
o Further away: no trace of change in membrane potential
 Few microseconds later: ion channels in the synapse already closed  membrane potential
returns to its resting state
o Ions that entered a few microseconds before still exerting effects on the membrane of
adjacent locations, but effect is becoming smaller
 Few microseconds later: effect is almost gone.
 Second input activated, arrives: effects on the membrane of the first input overlap with the
effects due to the second input
o Effects compound and add up  even larger depolarization
 Third input becomes active: overlap of responses  very large depolarization (sum of effects
from all 3 synapses combined)
 No more inputs are active; depolarisation spreads to the soma
o When it reaches the axon hillock, the depolarisation is enough to cross the threshold
and elicit an action potential in the postsynaptic neuron.
 Axon hillock: place in neuron with highest density of voltage-gated Na+ channels
o Hence usually where the action potential is normally initiated
o Located just at the intersection of the axon with the soma (initial segment of axon)
o Pay close attention at voltage here in that location to see whether a neuron will fire an
action potential.
 If depolarisation evoked by an activation of axon 1 not enough  cannot
cross the action potential threshold at the axon hillock.
 Direction-selectivity of summation:
o Direction 1: Summation causes depolarization
o Direction 2: Order of inputs reversed  neuron depolarizes much less  doesn’t
evoke action potential

Diffusion of voltage changes: action potential vs dendrites:

 Dendrites propagate changes in membrane potential
 o Depolarisation at one point in the membrane (eg. at synapse) diffuses passively along
the membrane
o No voltage-gated channels involved
 In dendrite, voltage moves symmetrically in both directions (towards and away from the
soma), since there are no inactivated channels causing a refractory period.

Information: measure of the reduction of uncertainty.

 Eg. In direction-selective neuron in retinal ganglion cells, the stimulus could be moving right
or not
o Arises out of summation of inputs across dendritic tree of neurons – sequential inputs
approaching axon hillock (visual stimulus moves in that direction) spatially-sum 
action potential; sequential inputs in opposite direction (visual stimulus moves in
opposite direction) sum away from axon hillock  absence of action potential
 Neuronal activity reduces uncertainty
o Fires: know stimulus was moving towards the right.
o Doesn’t fire: know there’s no stimulus moving to the right
 At any point in time, a neuron is either firing an action potential, or is not.
 Example:
o Background:
 Hypothetical neurons A and B with excitatory connections with a
postsynaptic neuron X Strength of each input: arbitrary magnitude of +1
 Threshold for neuron X to fire an action potential is 1 (one or more inputs
arrive  neuron X will be active)
 Binary code: firing = 1; not firing = 0
 4 Possible states of neurons A and B: Both quiet, both active, or either one
active
o Information:
 If X is active  at least one of A or B is active
 If threshold is 2 instead (achieved with neuron expressing less voltage-gated
Na+ channels, or putting the inputs of A and B in distant branches of the
dendritic tree)  both A and B must be active

Addition of inhibitory synapses:

 Remember: primary neurotransmitter used in inhibitory synapses is GABA.
o Neuron 1: excitatory presynaptic neuron.
o Neuron 2: inhibitory presynaptic neuron
o Neuron 3: receiving input from both neurons 1 and 2.
 Before any neurons are active, neuron 3 has a low baseline firing rate.
 Neuron 1 active  Neuron 3 starts increasing its firing rate.
 Both neurons are active simultaneously  inhibition counters effect of excitation; Neuron 3
remains silent

Time:
 Before: Input from excitatory neuron 1 and inhibitory neuron 2  no change in neuron 3’s
activity receiving input (excitatory effect is counteracted by the inhibitory effect)
 Add connection between the excitatory neuron and the inhibitory neuron
 Excitatory neuron 1 becomes active  activates both neurons 2 and 3
  Synapses not instantaneous  slight delay in the timing in which neuron 3 receives the initial
excitation, and the subsequent inhibition
 Neuron 3 will have period of high activity  cut after a brief interval when inhibition arrives
 Hence neuron 3 is carrying information about the state of neurons 1 and 2 on the time
dynamics of its responses

What information can we gather from hypothetical neurons A, B and C?

2.3: Different types of neurotransmitters

Glutamate and GABA – act as most common neurotransmitters in the nervous system
 Both amino acids; present primarily in central nervous system
 Effect of neurotransmitters:
o Glutamate: excites (common) or inhibits (rare) postsynaptic neuron  known as
excitatory neurotransmitter
o GABA: excites (rare) or inhibits (common) postsynaptic neuron  known as
inhibitory neurotransmitter
o Specific effect of a neurotransmitter depends on the specific ion channels opened by
the neurotransmitter and the specific ionic balance of the neuron
 Excitation and inhibition are in a constant balance in the nervous system: failure in balance
may lead to failures in function (eg. epilepsy).

Neuromodulators (neurotransmitters) - modified amino acids eg. acetylcholine, serotonin,

dopamine and norepinephrine (aka noradrenaline):
 Neuromodulation:
o Classic synaptic transmission: 1-to-1 effect of Glutamate and GABA (one presynaptic
cell excites one postsynaptic locally)
o Neuromodulators influence larger groups of neurons in a more diffused manner and
for a longer period of time.
 Unlike Glutamate and GABA, neuromodulators are not reabsorbed so
quickly  linger around and diffuse to other cells  affects larger area.
 Eg. noradrenaline (or norepinephrine), dopamine, serotonin and acetylcholine
 Act as excitatory or inhibitory neurotransmitters, depending on the receptor they bind to
Neuromodulator systems modulate activity of the central nervous system:
 Noradrenaline:
o Primary source: released by small nucleus in the pons (part of hindbrain), called the
locus coeruleus
o Small nucleus sends axons and creates synapses in multiple large areas of the brain,
including large parts of the cortex.
o Thought to increase arousal eg. when concentrating
 Dopamine:
o Produced by two small midbrain nuclei: substantia nigra and ventral tegmental area
o Distributed in large parts of the brain, including cortex and basal ganglia.
o Projections from ascending modulatory systems are diffuse and long-range
o They ascend (go from lower brain regions to higher ones) and release
neuromodulators
o Functional role: highly debated; generally thought to be important for the reward
system, motor system and cognition
 Eg. Parkinson’s disease: neurons in substantia nigra degenerate. People with
Parkinson’s develop motor and cognitive problems
 Serotonin:
o Raphe nuclei (small nuclei in brainstem) release serotonin, project to large areas of
the brain
o Thought to be important for the regulation of mood and sleep, among others
 Eg. Some of most well used anti-depressants: Selective Serotonin Reuptake
Inhibitors (SSRIs) - act by blocking the reabsorption of serotonin 
increases its concentration and duration in the brain
 Acetylcholine:
o Produced in small clusters of neurons - basal forebrain and pons; also project to
multiple areas in central nervous system.
o Thought to be important for learning, memory, reward, arousal, etc.
o Ascending neuromodulator systems: used to coordinate large parts of the brain to
accomplish something.
 Not very specific
 Neuromodulator systems modulate each other

Neuropeptides (eg. endorphins)

 Peptide: small chain of amino acids  more complex molecules
 Released by neurons, through the dendrites, soma and axon
o Previously mentioned neurotransmitters are exclusively released in axonal terminals
 Affect all nearby neurons that have appropriate receptors
 Molecules are involved in a number of brain functions, including analgesia (eg. endorphins),
reward, metabolism, memory, etc.
 Transfer of information: through release and diffusion around the neurons

Hormones: neurotransmitters that are released into the blood stream.

 Affect every tissue around the body that has the appropriate receptors
 Released by glands, (eg. pituitary gland, pineal gland), by organs (eg. pancreas, adrenal
medulla) and by fat cells in the body.
 Transfer of information: through release into the blood stream
Pre-Lecture 3: Neuroanatomy

3.1: Neuroanatomy

2 broad components of nervous system:

 Central nervous system (CNS)
o Composed by the brain and spinal cord
 Peripheral nervous system (PNS)
o Composed by everything else, including peripheral nerves and ganglia
 3 primary anatomical planes that transect (cut) the body:
o Parasagittal (divides the body between left and right)
 Sagittal cut: plane that cuts right through the middle of the body - left-right is
the only plane that shows symmetry
o Coronal (divides the body between front and back)
o Horizontal (divides the body between top and bottom)

Anatomical locations:
 Anterior (towards the head) / posterior (towards the stomach), also dorsal and ventral
respectively
 Cranial / caudal, also superior and inferior
o Standing person: cranial (up – towards the head), caudal (down)
o Inside the head: superior, inferior
 Distal (away from centre of body) / proximal (towards centre of body)
 Medial (close to midline) / lateral (away from midline)
 Left / right

Brodmann noticed that different areas of the brain had different “signatures”.
- Some areas had a high density of neurons, or some of them had very thick layers of neurons
within a patch of cortex
- Drew boundaries to areas of homogeneous characteristics, numbered each
- Different areas tend to have different functions
- Renamed to eg. dorsolateral prefrontal cortex (area 46), primary visual cortex (area 17)

Gross (macroscopic – seen without microscope) anatomical structures in CNS:

 Gyrus: protuberance on the surface of the brain.
o Many gyri on lateral surface of brain
 Sulcus (p: sulci): fold / groove that separates one gyrus from another
o Fissure: long and deep sulcus
 In the brain:
o Nerve (set of axon in the periphery):
 originates from central nervous system to a muscle or gland
 originates from sensory organ to the central nervous system
 Becomes a tract / projection when entering the brain
 Structure A projects to B: neurons with cell bodies located in A have
axons that extend to B, and synapse onto neurons located in B
 Ganglions: clusters of neuron cell bodies (somas) outside the central nervous system eg. next
to spinal cord
 o Nucleus (nuclei): ganglion located inside the brain

3.2: Anatomy of central nervous system

Components of CNS:
 Brain: nervous tissue contained inside the skull
 Spinal cord: nervous tissue contained inside the spine
 PNS composed of ganglia and nerves outside the CNS
o Ganglia: groups of cell bodies clustered outside the CNS
o Nerves: bundles of axons that connect the CNS with the rest of the body

Another form of CNS composition:

 Gray matter: where cell bodies of neurons are located
o Also have axons, which never leave to communicate with neurons nearby
 White matter: where the axonal fibres of these neurons are located
o Axons that go through here need to reach far-away regions
 Spinal cord: Gray matter in the centre is surrounded by white matter
 Cortex: Gray matter is outside and white matter inside

3 primary subdivisions of the brain (from posterior to anterior):

 Hindbrain: comprises brainstem and cerebellum
 Brainstem: comprises medulla, pons and reticular formation
 Midbrain
 Forebrain

3.3: Anatomy of hindbrain and midbrain

Hindbrain: comprised by the brainstem (medulla, pons, reticular formation) and cerebellum
 Brainstem: most caudal section of the hindbrain, autopilot of our bodies
A number of the nerves that form the peripheral nervous system originate in nuclei of the
brainstem
o Medulla (medulla oblongata): above spinal cord
 Tons of small nuclei around the brainstem, each with a different function
 Taste processing (only sense that is processed in the medulla), also
first sense evolved
 Chemical sensing in all living organisms, including the most ancient
bacteria.
 Control of blood-vessel dilation (eg. Hot  blood vessels dilate to
dissipate heat)
 Centres for respiration are also here (eg. More frequent breathing
during exercise controlled by a nucleus in the medulla
 Control of intestinal movements, motor coordination, control of heart
rate, vomiting, salivation, coughing and sneezing: controlled by
different nuclei in the medulla
 Summary: involved in multiple important autonomic (or involuntary)
functions - keeps us alive automatically
 o Pons: small ball of higher cell density than the surrounding reticular formation and
midbrain; clear bulge in brainstem
o Pons and reticular formation: number of functions including control of respiration,
sleep, swallowing, bladder, equilibrium and posture, eye movements, facial
expression, as well as some sensory functions related to taste, hearing and facial
sensation
 Summary: involved in multiple important autonomic (or involuntary)
functions, in addition to some sensory processing
 Cerebellum:
o Involved in motor control (fine movement, equilibrium, posture, motor learning etc).
o Damage to this area  condition: cerebellar ataxia
 Eg. No difficulty controlling right arm, but hard time keeping his left arm
straight (reaching his nose and staying there)
 Not a failure to generate movements, but more like a failure to balance and
coordinate his movements
o May be involved in cognitive function (attention, language, etc), not well established

Midbrain:
 On top (anterior / towards the face): cerebral peduncles - axon highway that communicates
the forebrain with the hindbrain and spinal cord
o Big parts of these structures devoted to axon fibres to communicate distant areas
 Functions include: visual processing (generation of eye movements, processing of visual
information related to visual reflexes), auditory processing, oculomotor processing
 Dopaminergic ascending modulatory signals generated here (where substantia nigra and
ventral tegmental area are located - main source of dopamine in the brain)
 Selective degeneration of these neurons leads to motor symptoms in Parkinson’s disease (Eg.
cannot stretch arms and keep them still)

3.4: Anatomy of forebrain

Primary divisions:
- Cerebrum: comprises cerebral cortex, hippocampus, basal ganglia and olfactory bulb
- Thalamus

Cerebral cortex (in cerebrum):

 Largest part of brain; grey matter of brain
 Well-defined layer of neurons that folds, forming the gyri and sulci of the brain
 Summary of functions: perception, cognition and action (sensory, cognitive and motor
processing)
 Divided into 4 hemispheres; large central sulcus and Sylvian fissure separates them
o Frontal lobe: everything anterior to the central sulcus
 Involved in movement control, decision making and short-term memory
o Temporal lobe: under the sylvian fissure
 Involved in auditory processing and advanced visual processing
o Parietal lobe: posterior to the central sulcus, dorsal to the temporal lobe
 Involved in body sensations, such as touch processing, and it is involved in
advanced visuospatial processing
 o Occipital lobe: most posterior part of the brain
 Primarily involved in the early stages of visual processing
 No clear landmark in the brain separates the occipital, parietal and temporal lobes
 Bone plates in the skull define the 4 lobes

Hippocampus (in cerebrum):

 Small tube that wraps the base of the forebrain; recognised by its spiral shape
 Referred as the middle temporal lobe (located in medial section of the temporal lobe)
 Involved in memory consolidation and spatial navigation (*Memory)

Basal ganglia (in cerebrum):

 Located lateral to the thalamus, and medial to the cortex
 Nuclei right at the centre of the brain
 Comprised by 3 main structures
o Dorsal striatum
 Comprised by the caudate and putamen
 Functions include control of voluntary movements, procedural learning,
cognitive control and emotional processing
 Functions supported by dense connections with the frontal lobe
o Ventral striatum
o Globus pallidus

Olfactory bulb (in cerebrum):

 Right on top of the nasal cavity
 Receives olfactory information
 Very small in humans; much larger in other animals that rely more on olfaction

Thalamus: right at the centre of the brain

 Connects brainstem with forebrain
 Composed of multiple nuclei (lateral geniculate nucleus, medial geniculate nucleus, pulvinar,
mediodorsal nucleus etc)
o Tightly packed; each serves a different function
o Lateral geniculate nucleus is the first region to receive input from the retina
o Medial geniculate nucleus receives auditory information

Other areas in the forebrain – small nuclei around the thalamus

 Hypothalamus, epithalamus, subthalamus
 Involved in multiple things including neuroendocrine control, circadian rhythms, regulation
of emotions, etc
 Together with thalamus, are a number of nuclei at the centre of the brain that connect the
cerebral cortex with other brain and peripheral regions and control the connections between
the cerebral cortex and the rest of the nervous system

3.5: Cranial and autonomic nerves

Spinal and cranial nerves

 Spinal cord has spinal nerves
  Medulla, pons, midbrain and thalamus have 12 pairs of cranial nerves that fulfil different
functions
o Cranial nerves connect brain structures with peripheral structures (eg. muscles,
sensory organs, glands)
o Nerves are named 1 to 12 from more anterior to more posterior
 1: connects olfactory receptors in nose to olfactory bulb
 2: optic nerve; connects eye to lateral geniculate nucleus of thalamus
 3,4 & 6: involved in controlling eye movements (position and pupil dilation)
 5: involved in skin perception and control of the jaw
 7 & 9: involved in mouth sensation and movements
 10: vagus nerve; main parasympathetic nerve innervating most organs
 11: involved in the control of neck and shoulder movements
 12: involved in the control of muscles of the tongue

Sympathetic and parasympathetic nerves

 Together with associated ganglia form the autonomic nervous system, since they control
autonomic / unconscious functions
 Sympathetic NS: activating system
o Increases the heart rate, blood pressure, respiration rate, etc
o Dominant in stressful situations (eg. decide fight or flight response when threatened)
o A network of ganglia (near spinal cord) contains cell bodies of neurons that form the
multiple nerves that innervate different organs
o Ganglia close to the spinal cord; long postganglionic nerves innervate organs
 Parasympathetic NS: counteracts sympathetic NS
o Dominant during relaxed states
o Vagus nerve (cranial nerve 10): main nerve of this system
 Branches into most organs, except for those found more posteriorly (eg.
bladder / uterus receive parasympathetic inputs from the pelvic nerve instead)
o Long axons sent through vagus and pelvic nerves to ganglions located right inside, or
very near, the target organs - vagus and pelvic nerves are preganglionic.
 Sympathetic NS: composed of sympathetic ganglia near the spinal cord and nerves that
connect to body organs, involved in preparing the body for stressful situations;
Parasympathetic NS: composed of parasympathetic ganglia near the organs and small nerves
that connect to the organs, involved in relaxing the body
3.6: Research methods in neuroscience

To gain a full understanding of the function of the brain, and how it relates to the mind, need to know
physical structures that underlie computations performed by the brain
 Sub-cellular level: studying the structure of components smaller than the cell
o Eg. Studying dendritic integration - study activity in a single dendritic spine.
o Electron microscopy used to study connectome (comprehensive map of the
connections of the brain at the level of individual synapses)
 Connectome: wiring diagram of the brain.
o Study used large-scale reconstruction of physiologically identified neurons using
electron microscopy.
 Individual cell level to study anatomy
o Eg. Golgi staining method: randomly stains a small sub-set of neurons.
o Sparse staining allows to distinguish individual neurons in the tissue
o From electron microscopy studies - density of neurons is very high, so if all neurons
stained, almost impossible to disentangle different neurons and analyse their
morphology.
 Systems level: studying how brain systems are organised
o Eg. visual system
o Eg. Technique: neuronal tracer studies of connectivity between areas.
 Inject a few small drops of solution that contains neuronal tracer into a brain
 Let animal recover; wait for 1 or 2 weeks.
 Tracer gets absorbed by the neurons in contact with it – by cell bodies and
axons
 Absorbed molecules slowly transported to the rest of the neuron, including
soma, dendrites and axons
 After 1 or 2 weeks, any neuron in the brain labelled by this tracer will project
to (sends an axon) the site of injection
 With one simple injection, can get a full map of every neuron that sends
projections to a region of the brain
 Whole brain level: eg. use magnetic resonance imaging to study whole-brain axonal paths
MRI scanner was used to determine the locations of large axon paths in the brain
o Only level of analysis that is non-invasive - don’t need to cut on tissue to take
measurements  very popular to study human populations

Physiology of nervous system: methods to study function of nervous system

 Cellular level eg. intracellular recording techniques to study excitation and inhibition in single
neurons.
o Method:
 Get very thin glass electrode in contact with membrane of the neuron
 Pipette punctures the membrane, starts measuring the voltage differences
between the inside and outside of the membrane.
 Used to understand membrane potential properties, including resting
membrane potential and action potential
 Systems level: study the action potential activity of thousands of individual neurons across
multiple brain areas
 o Method:
 Insert very thin metal microelectrodes into the brain tissue, get electrode tip
(measures changes in voltage) very close to soma of the neuron
 When an action potential is fired by the neuron, the movement of ions outside
the cell will create a change in voltage that is measurable with these
electrodes
 Many of these arrays can be implemented for multiple years to measure the
activity of multiple cells across multiple areas
 Studying activity of populations of individual neurons: 2-photon calcium imaging
o Method:
 Genetic modification is done to neurons, so they express a protein
 Protein emits fluorescence when in contact with Calcium
 Calcium found in very low concentrations normally inside the cell, during
action potential, calcium enters briefly into the cell  calcium sensor starts
fluorescing
 Microscope mounted on top of the brain measures this brain activity (eg.
patch of visual cortex expressing calcium sensors – direction-selective cells)
 Whole-brain level: most commonly used technique is electroencephalography (EEG)
o Method: One or more electrodes are placed on the head (outside the head, unlike
microelectrode arrays)
 Electrodes measure changes in voltage
 EEG signals can be collected with one electrode, eg. in commercial system
used for gaming
o Examples of measuring EEG: Trace can be taken from an electrode when the person
is (i) excited, (ii) relaxed, (iii) drowsy, (iv) asleep, (v) in deep sleep
 Depending on the state, the frequency (how fast the voltage fluctuates) at
which the signal oscillates changes
 Alpha, beta, gamma and delta frequencies have different ranges (sleep)
 More excited  higher frequency of oscillation, smaller magnitude of
changes in voltage
 Deep sleep  slow frequencies dominate the signal; huge oscillations
 Signal interpreted as a degree of synchrony in activity of underlying brain
tissue
 Millions of neurons activating around the same time  one of the electrodes
may see small deflection in voltage; 10 million neurons active simultaneously
 larger change in voltage observed.
 Small oscillations + high frequency in most alert state - each cell doing its
own thing, processing its own information - not synchronised to other nearby
neurons
 Deep sleep: large parts of the brain go through waves of activity and silence
together; not much processed under these conditions, because all neurons
following the crowds
o EEG signal vs signal obtained with microelectrode recordings: EEG sees more of
activation / activity of brain regions in response to stimuli. Microelectrode recordings
see the activity of a single cell, but don’t know about overall activity of brain
 Functional magnetic resonance imaging (fMRI) Does not measure brain activity directly, the
blood-oxygen-level dependent signal (BOLD)
 o Stimulus arrives (eg. light shined)  activates neurons  neurovascular coupling
(neuronal activity triggers a dilation of blood vessels near the active neurons) –
primarily driven by interaction between the neuron and glia cells, which in turn
interact with capillaries in the vicinity.
o fMRI measures changes in level of oxygenation in blood
 Blood vessels dilate  more blood flows in that region  more oxygen in
the area, because blood carries oxygen to the tissue
 This change in oxygen is detected by the MRI scanner  transformed into a
pattern of oxygenation of different voxels (or 3 dimensional pixels) in the
brain
o Displaying of fMRI data
 Separate scan with higher resolution taken to show the anatomy of the brain
 See areas that showed higher activation in one condition compared to another
(unlike EEG / microelectrode recordings, fMRI data only makes sense when
comparing one condition with another (eg. with visual stimulation vs without
visual stimulation)
 Cannot assess whether an area is active above zero, but can assess whether
the area is relatively more active in one condition compared to another
o Other ways of displaying same data
 Lateral surface view of brain to monitor activation: can see whole surface,
but not what happens inside sulci (hidden from view)
 Superimpose activation maps on inflated brains
 Cortex is a continuous surface – can be inflated so deep sulci come to the
surface
 Hence data can be displayed in higher detail (but still cannot = display
activations in sub-cortical areas)
o EEG and fMRI are non-invasive  most commonly used to study human physiology

Methods to manipulate brain activity

 Different techniques offer different levels of resolution
 Micro-stimulation (metal extracellular microelectrodes): measure neuronal activity
o Method: Inject current through the electrodes  evokes activation in neurons near the
tip of the electrode
o Eg. Deep-brain stimulation (DBS)
 Patient with Parkinson’s disease and problems with motor control due to
degeneration of midbrain dopaminergic neurons
 Implanted with an electrode in the brain (used to inject current in a specific
part of the brain, eg. basal ganglia)
 When electrode injects current, patient is able to control his hands well
 Transcranial magnetic stimulation (TMS): non-invasive technique
o A magnetic coil placed on top of a region of interest
o TMS pulse over motor cortex used to disrupt movement  place of interest (eg.
hand) moves slightly during the pulse
 Transcranial direct current stimulation (tDCS): non-invasive
o Inject current through electrodes somewhere in the surface of the head
 Non-invasive techniques have a lower specificity than the invasive technique; benefit: can be
used in healthy humans to study cognition
Pre-Lecture 4: Vision I

4.1: Anatomy of the eye

Important structures:
 Eye is composed of neural (retina) and non-neural tissue (rest of the eye)
 Optic nerve: initial segment of the nerve that connects the eye to the rest of the brain
 Optic disc: Point in which the optic nerve exits the eye / retina; lacks retinal tissue
 Retina: Nervous tissue (neuronal layer) that covers the back surface of the eye
 Iris: coloured area of the eye
 Pupil: Hole left by the iris in the centre of the eye
 Cornea: front of the eye; can be touched with the finger
 Lens: large structure used to distort light entering the eye to focus it on the retina
 Fovea: area of highest concentration of neurons

Optic disc:
 Neurons in retina AKA retinal ganglion cells: send their axons to the brain, forming the optic
nerve
 Part of retina where axons of retinal ganglion cells exit the eye – zone with no neurons
(photoreceptors) – blind in that part of space that falls onto that spot of retina (blind spot)
o Light entering falls within the optic disc  cannot see
o Both eyes face forward  both eyes receive light from overlapping parts of space 
blind spot has little bearing on our visual capacities

Retina:
 Anterior part of retina (faces the is the front of the eye towards the pupil, where light enters)
to posterior part of retina (back of the eye, connecting to optic nerve) – 3 layers containing
neuron types:
o Ganglion cell layer: Ganglion cells
o Middle layer: Bipolar, amacrine and horizontal cells
o Photoreceptor layer: Photoreceptor cells
 Light enters, has to cross the first 2 layers before reaching photoreceptors
 Photoreceptors synapse onto bipolar cells  bipolar cells synapse onto ganglion cells;
ganglion cells are output cells of the retina, sending axons into the brain through the optic
nerve
o Optic nerve is composed of axons of retinal ganglion cells
  Connects retina to rest of the brain
 Horizontal and amacrine cells have side connections
o Important modulators of the activity of photoreceptors, bipolar and ganglion cells
o Horizontal cells help combine activity of multiple photoreceptors in bipolar cells
 To compute presence of specific contrast difference across small portion of
bipolar cell’s receptive field
o Amacrine cells help combine activity of multiple bipolar cells in retinal ganglion cells
 To compute contrast changes across receptive fields, or movement of stimuli
in a specific direction within their receptive fields
 Each of the 5 neuron types can be subdivided into sub-classes based on morphology and
physiology (neurons with different dendritic morphology have different physiological
properties):
o 3 kinds of cones
o 2 kinds of horizontal cells
o 10 kinds of bipolar cells
o 24 kinds of amacrine cells
o 10 kinds of ganglion cells

Fovea: dark spot in the eye; part of retina is possessing highest density of neurons (photoreceptors)
 Since light must cross ganglion/bipolar/amacrine/horizontal cell layers before reaching the
photoreceptors, this tissue may distort the light crossing, affecting vision
o Hence fovea has a morphological specialisation – most of the tissue is pushed to the
sides, allowing light to go straight to the photoreceptors in this area
o Cell bodies of non-photoreceptor neurons displaced to the sides, allowing light to
reach photoreceptors more directly
 Cones tightly packed in fovea since rods are absent
o Density of cones is very high, but very quickly becomes extremely low
o Rods virtually absent, but around the fovea (parafoveal area) – highest density of rods
 Rods and cones have different ranges of luminosity / light intensity over which they work
o Cones have lower sensitivity  strong light (eg. daytime), activity reflects changes in
luminosity; completely quiet at night
o Rods: Hypersensitive when luminosity is very low (eg. nighttime) – modulate activity
based on small changes in luminosity; saturated in bright light  small changes in
luminosity do not affect their activity
o Hence during the day, place object to straight on fovea; at night – look at a location
adjacent to the object, so light from falls on the parafoveal region containing highest
density of rods
 Part of retina in periphery (region receiving light from far away from focus):
o Very large cones
o Smaller rods – cones in the fovea are much smaller than in the periphery: hence high
resolution at the fovea, poor resolution at the periphery
 Moving away from fovea
o High density of cones in the fovea quickly drops
o High density of rods in the parafovea, which drops both in the fovea and in the
periphery
 Summary: Cones denser in the fovea in fovea and almost absent in periphery; rods denser in
parafoveal region, absent in fovea itself
4.2: Phototransduction

Phototransduction:
- Photo = light; Transduction = conversion from one type of energy to another
Phototransduction: conversion of electromagnetic energy (or light) into electrochemical
energy (or cell polarisation) in neurons
- Photoreceptors in brain carry out phototransduction
- Outer segment of a rod: composed of many tightly packed membranes, stacked one on top of
the other (same bilipid membranes that form the cell membrane, but located inside the cell)
- Rod’s cell membrane + stacked membranes of outer segment (where proteins called
rhodopsin molecules are embedded)
- Rhodopsin (photopigment) sits in inner membranes
- Small molecule in the middle of rhodopsin protein: retinal
- Configuration: C atoms marked with 11 and 12, bound H face the same direction (cis
molecule)  11-cis retinal

Process:
 Light enters eye  photon may hit one of retinal molecules  absorbs energy of photon 
Energy makes retinal molecule twist a little  rhodopsin molecule needs to change
configuration to accommodate newly shaped retinal molecule inside
 New configuration: H atoms on opposite sides of molecule (trans molecule), hence in retinal –
called all-trans retinal  change in configuration (driven by absorption of one photon)
triggers cascade of events leading to vision
 Other factors: Membrane of the rod contains open ion channels, small cyclic GMP molecules,
membrane proteins around the newly activated rhodopsin molecule

 Dark: ion channels in the membrane allow the entry of positively charged ions  membrane
of photoreceptor is depolarised  photoreceptors become more active (release more
neurotransmitters)
o Photoreceptors are one of the few neurons that don’t generate action potentials, but
instead release neurotransmitters in their synapses proportionally to how depolarised
the neuron is
 Transducin: one of the molecules in the membrane attracted to rhodopsin, only when
activated by the absorption of light
o GDP is bound to this protein (GTP is also an energy source)
o Transducin binds to the activated rhodopsin molecule  exchanges its GDP for a
GTP  cleavage of transducing  alpha subdomain (bound to GTP) then binds to
phosphodiesterase (another membrane protein)  activation of phosphodiesterase,
which converts cyclic GMP floating around into GMP
o Even cGMP attached to ion channel in the photoreceptor membrane is converted to
GMP
o Since channel needs to be attached to a cyclic GMP to remain open, ion channel
closes, positive ion flow stops
 Effect on membrane of neuron:
o Inward current of positive ions depolarises neuron
 o Constant potassium current (like in other neurons) through K+ selective channels –
voltage across the membrane just below zero, quite depolarized compared to normal
neurons at rest (around -70mV)
o Level of depolarisation  release of neurotransmitter from photoreceptor
 Light absorbed by photopigment embedded within transmembrane protein located in stacked
membranes within outer segment of cell  cascade of biochemical events  closure of the
multiple cation-selective channels in the membrane  membrane now dominated by outward
current of K+  cell is hyperpolarised  decrease in the release of neurotransmitter
o Cation-selective channels increase conductance of Na+, K+ and Ca++ when open 
membrane potential more positive than reversal potential of K+  depolarized
membrane leads to large release of glutamate
 Summary: Light inhibits photoreceptor activity – Rhodopsin in photoreceptors (opsins)
absorb photons of light change in configuration  biochemical cascade  closure of
membrane cation-selective channels  voltage of membrane dominated by conductance of
leak K+ channels  hyperpolarisation of cell / photoreceptor  less release of
neurotransmitters by photoreceptors – all photoreceptors have OFF receptive fields

Amplification of phototransduction signal:

 For every rhodopsin activated, 800 transducin molecules cleaved
 For every transducin molecule cleaved, one phosphodiesterase that becomes active  800
become active
 Hence around 4800 conversions of cyclic GMP to GMP  closure of roughly 200 ion
channels
 One photoreceptor closes hundreds of ion channels through signal amplification  higher
sensitivity to light

4.3: ON and OFF responses in the retina

Definition:
- Cones and rods (photoreceptors) decrease their activity when light hits them, increase their
activity when the light is turned off
o OFF response: increase in responses to decreases in light
- Bipolar and ganglion cells can increase or decrease their activity when light turns on, so can
have ON or OFF responses
o ON response: increase in response to increases in light
Bipolar and ganglion cells:
 Photoreceptors synapse onto bipolar cells, which synapse onto ganglion cells
o Bipolar cells have receptive fields with centre-surround organisation
 Lights off: photoreceptors depolarised, releasing neurotransmitters
 Photoreceptors release glutamate (most common excitatory neurotransmitter in the brain) 
glutamate receptors expressed by bipolar cell determines type of receptive field
 Bipolar cells expressing ionotropic (sign preserving) glutamate receptors
o Glutamate binds to receptor  neuron depolarises
o Bipolar cells increase their activity in response to decreased light  OFF bipolar
cells
o OFF bipolar cell synapses onto (excites) a ganglion cell  OFF ganglion cell
o OFF responses occur in bipolar cells with ionotropic glutamate receptors (sign-
preserving synapses)
 Bipolar neurons expressing metabotropic (sign reversing) glutamate receptors
o Receptors close Na+ channels  hyperpolarisation of the neuron
o Bipolar cells increase their activity in response to increased light  ON bipolar cells
o ON bipolar cell synapses onto (excites) a ganglion cell  ON ganglion cell
o ON responses occur in bipolar cells with metabotropic glutamate receptors (sign-
reversing synapses)

4.4: Centre-surround organisation

Receptive field of an individual sensory neuron: region of space over which a stimulus will trigger a
response in the neuron
 Animals don’t have receptive fields, sensory neurons do
 One neuron in retina: only objects located in specific area of space activates the neuron
 All neurons in the visual system (not just photoreceptors) have receptive fields, not just
photoreceptors
 Deeper into the brain, larger receptive fields
 Experiment:
o 1 neuron recorded in primary visual cortex (monitored through metal microelectrode
inserted)
o Animal asked to fixate on a spot, where bars of light are flashed
o Cell increases activity when bar flashed in that location, but no activity next to it
o Receptive field of neuron recorded is the spot
o Moving eyes around  receptive fields move around
o Receptive field defined with respect to where the animal is looking at

Organisation in receptive field – Centre-surround organisation

 Neuron with receptive field: stimuli / light in this area affects activity of the neuron; stimuli
elsewhere does not
 Has centre with one response property, and area surrounding centre with opposite response
property
 Visual stimulation excites neurons that have receptive fields overlapping with the stimulus
location
  Activity of neuron does not change if changes in luminosity are homogenous across whole
receptive field (excitation due to full-field illumination of ON-centre OFF surround =
inhibition due to OFF-surround effect)
 ON-centre OFF-surround: light in the centre excites the cell; light in the surround inhibits the
cell
o No light: darkness activates surround, inhibits the centre – cell relatively silent
o Shine light in centre only: neuron responds strongly by increasing firing rate
o Make light bigger (eg. whole bright wall): smaller cell activity, since excitation in
centre countered by inhibition by light in surround
o Centre occluded (least preferred stimulus): neuron inhibited
 OFF-centre ON-surround: light in the centre inhibits the cell; light in the surround excites the
cell

Mechanism generating centre-surround organisation in retina

 Monitor activity of horizontal cells
 Cone in the centre synapses onto bipolar cell – bipolar cell excited by light  inhibitory
synapse; ON centre bipolar cell
 Cone on right synapses onto horizontal cell, which synapses onto cone in the centre,
inhibiting it. Light falls on centre  bipolar cell excited; in surround  bipolar cell inhibited
 Dendrite of horizontal cell serves as pre- and post-synaptic terminal: can release
neurotransmitters onto the cone, and detect neurotransmitters released by the cone
 Summary: centre-surround is organised by inhibiting the centre photoreceptor via horizontal
cell activity
 Process 2: Light falls on cone in centre of bipolar cell receptive field  cone decreases
release of neurotransmitters  depolarisation of bipolar cell with ON-centre OFF-surround
receptive field and expresses metabotropic receptor (hyperpolarises cell when binding to
neurotransmitters)  increases release of neurotransmitters by bipolar cell
 Light falls on cone in surround of bipolar cell  cone decreases release of neurotransmitter
 decreased activation of horizontal cells it connects to  decrease of inhibition provided by
horizontal cell onto centre cone (since horizontal cells have inhibitory effects over cones) 
centre cone depolarises  releases more neurotransmitter  hyperpolarisation of bipolar cell
 decrease release of neurotransmitters

4.5: Colour vision

Electromagnetic spectrum:
 Gamma rays (smallest wavelengths / frequencies; smaller than one tenth of a nanometre)
 Visible light spectrum: narrow range of frequencies between 300 and 750 nm
o Just below (ultraviolet) and just above (infrared) not visible to humans, but some
frequencies can be detected by animals with their photoreceptors
 AC circuits, AM radio, TV signals transmitted through antennas, FM radio frequencies, etc.
 Only cones active in high luminosity conditions, rods are active in very low lighting
conditions  only focus on activity of cones in colour vision
 3 types of cones (1 type of rod)
o Medium-wavelength cone: responds maximally to wavelengths around 520nm
(commonly perceived as green), sometimes called green cone (but may be perceived
as non-green colours)
 o Long-wavelength cones: maximally responsive to wavelengths around 580nm
(normally perceived as yellow), sometimes called red cones – only ones with some
sensitivity in the side of the spectrum above 650nm (normally perceived as red)
o Short-wavelength cones
 Determining wavelength of light falling onto 3 cones:

o Cell 1 (long-wavelength) active at 27% of maximum activity; Cell 2 (medium-

wavelength) at 35%; Cell 3 (short-wavelength) active at 70%
o 450nm is wavelength where all 3 cones converge
 Long and middle-wavelength cones far more common than short-wavelength cones
 Can be significant differences in the distributions across different people, arrangement seems
semi-random, but differences translate into differences in colour vision
 Activity of cone – information about presence / absence of light of specific wavelength in
receptive field
 Trichromatic Theory of Colour Vision: colours of light are determined by the relative rates of
response of the 3 photoreceptor types

Opponent-Process Theory: we perceive colour in terms of opposites – one continuum from red to
green, another from blue to yellow
- 3 separate channels for vision: black/white, red/green and blue/yellow
- Channels in retina – some cells excited by red and inhibited by green, or vice versa
- Red-green: long- and medium- wavelength cones have opposing effects – more red means
more green, and vice versa
o Neurons in the red-green channel: no information about blue and yellow
- Yellow-blue: long- and medium-wavelength cones combine to counteract short-wavelength
cone

Retinex theory: Cortex compares information from various parts of the retina to determine the
brightness and colour for each area
- Defined in cortex by the interaction between wavelength of an object the wavelengths of its
surround
- Other two theories only consider effect of wavelength emitted by the object, ignores the
context of the wavelength
- Context also affects brightness perception
- Perception of color and brightness are not a property of objects, nor a property of the light
Pre-Lecture 6: Audition

6.1: Sound Waves and ear structure

Audition: sensation of periodic compressions (or oscillations) of air, water or other media
 Compressions:
o Described by frequency (cycles per second)
o One cycle per second = 1 Hz
o Frequency is related to pitch: low frequencies = low pitches; high frequencies = high
pitches
o Children can hear higher frequencies than adults; lose ability over time sense high
frequencies due to the exposure to loud noises damaging our ears
 Described by amplitude (magnitude of wave measured from peak to trough)
o Loudness of a sound is related to its wave amplitude, measured in decibels
 Sounds: described by pitch (determined by wave’s frequency); loudness (determined by
wave’s amplitude, and timbre (tone colour / quality)
o Timbre: relates to other secondary frequencies present in a signal – can hear single
pitch, but signal is a mixture of multiple waves, with one that dominates (highest
amplitude)
 Timbre of the same note played on different instruments have different sets
of secondary frequencies associated with main frequency
o Sound can have a certain pitch and loudness, yet have a different timbre

Structure of the ear

 Outer ear
o Pinna: structure responsible for altering the reflection of sound waves; helps us locate
source of sounds in the vertical axis (sound localisation)
o Auditory canal
 Middle ear:
o Tympanic membrane / ear drum: membrane that connects the outer and middle ear;
vibrates when struck by sound waves, and moves 3 tiny bones of the middle ear
o Air-filled area with 3 tiny bones moved by the tympanic membrane, that amplifies
this movement, then moves oval window (on the other side) connecting the middle
and inner ear
o Eustachian tube: connects middle ear with the mouth cavity; outer and middle ear
filled with air
o Diving under water  high water pressure pushes tympanic membranes and causes
pain  equalise by blowing air from lungs while covering nose, to increase the
pressure inside the middle ear  overpower increased outside pressure  relief the
pain
 Inner ear:
o Where auditory receptors are located
o Cochlea: snail-shaped structure; contains auditory receptors and mediates audition
o Semicircular canals: mediate balance

6.2: Cochlea and mechanotransduction

  Cochlea (in inner ear):
o 3 tiny bones (middle ear) vibrate with sound  move oval window membrane
(vibrates)  liquid which fills 3 chambers of the cochlea vibrate  vertical
movement of basilar membrane at frequency and amplitude of sound vibrations,
moving hair cells up and down
o Organ of Corti (inside middle chamber):
 Hair cells (sensory neurons)
 Top of cells contain little hairs; surface structure shows dozens of
hairs neatly organised next to each other, arranged in order of
decreasing size
 Several line up along length of cochlea
 Multiple hairs on surface joined by tiplinks (molecular chains)
 Carry out mechanotransduction
 Two membranes
 Basilar membrane (on the base)
 Tectorial membrane (on top)

Mechanotransduction in hair cells

 Mechano = mechanical (movement); Transduction = conversion of energy from one type to
another
Mechanotransduction: conversion of mechanical energy (movement) into electrochemical
energy (cell polarisation) – auditory equivalent of photoreceptors in retina
 Sound waves contact outer ear  captured by pinna, bounced into auditory canal  contact
middle ear  vibrations in the air converted into vibrations of the tympanic membrane 
move 3 tiny bones (hence amplifies vibration)  move oval window membrane of cochlea 
generation of action potentials in the auditory nerve
o Vibrations of tympanic membrane according to sound amplitudes and frequencies
 Cochlea: tube that rotates in a spiral  can see so many different chambers
 Organ of Corti with hair cells all along the spiral
o Hair cells excite ganglion cells that generate auditory nerve
 In retina: ganglion cells form optic nerve (ganglion: structure that sends
projections to another area)
 Movement of liquid in chamber of Organ of Corti moves the membrane up and down: same
frequency as the sound frequency; amplitude proportional to the sound amplitude
 Movement generates deflection of cilia at the top of the hair cell (tectorial membrane laying
on top of them)
 Liquid that bathes the middle chamber is very high in K+ (higher than concentration in the
cell), base of hair cell bathed in more normal, low K+ solution
o Reversal potential of K+ is positive rather than negative
 Sound wave pushes the membrane up  deflection to the back  tiplinks that connect
different cilia pull the membrane of cilia below
 Pulling opens ion channel that is selective to potassium  mechanical force translated into
electrochemical force
 Opening of K+ channels  cell depolarises (due to positive K+ reversal potential)
 Depolarisation propagates to base of the cell, where voltage-gated calcium channels open 
calcium entering cell triggers release of neurotransmitters onto the ganglion cells
 K+ channels at the base open, allow exit of K+ down the concentration gradient; hair cell
hyperpolarised  release of neurotransmitters stopped
  Cycle of depolarisation (when sound wave pushes membrane up) and hyperpolarisation
(when it goes down)  action potentials in auditory nerve
 Summary: Mechanotransduction by hair cells converts fluid vibrations into action potentials
by opening mechanically-gated K+ channels near the hairs of the cells, depolarising the cell
(Since extracellular fluid around the tip has a higher concentration of K +)

Damage of delicate hair cells:

- Person turns deaf
- Treatment of restore audition: cochlear implants
o Array of electrodes slowly pushed through chambers to electrically stimulate
different sections of the cochlea
o Microphone placed in outer ear converts sound waves into pattern of electrical
stimulation in electrodes  stimulate auditory nerve

6.3: Audition neural pathways; determination of pitch and location of sounds

Auditory pathways in the brain:

 Signals from cochlea  ipsilateral cochlear nucleus in brainstem  crosses to the
contralateral superior olive in the brainstem  inferior colliculus in midbrain  medial
geniculate nucleus in thalamus  primary auditory cortex in temporal lobe (before last step,
all sub-cortical structures)
o Visual system: thalamus also projects to the primary sensory cortex – signals from
left ear are processed by right cortex, and vice versa
 Primary auditory cortex: tonotopic map (map of tones) – more anterior portions process
deeper sounds (low pitch sounds), more posterior portions process higher pitches
 Secondary auditory cortex surrounds it, performs more advanced processing of auditory
signals
 Auditory system: damage to the primary auditory cortex does not lead to deafness, leads to
inability to discriminate different pitches, among other deficits
o Visual system: damage to primary visual cortex leads to blindness

Theories of pitch perception:

 Frequency theory
o Basilar membrane (where hair cells rest) vibrates in synchrony with sound, causes
auditory nerve axons to produce action potentials at the same frequency as the sound
(Cells activate on every cycle)
o Best explains low frequency sounds (below 4000Hz)
 Place theory
o Each area along the basilar membrane has hair cells sensitive to only one specific
frequency of wave (Different portions of the cochlea vibrate with different
frequencies, selectively activating hair cells in that area)
o Know source of activity in cochlea  can find out pitch
o Best explains high frequency sounds (above 4000Hz)
 How can auditory nerve activate with frequencies of up to 4,000Hz if refractory period of a
neuron allows it to respond at most at 1000Hz?
o Different neurons respond at different cycles of sound wave
 o Overall, considering all neurons, auditory nerve becomes active 4000 times per
second (even if this exceeds the capacity of individual neurons)

Sound localisation:
 Horizontal axis:
o Method 1: use sound shadow to determine the location of sounds
 Head creates shadow when a sound comes from a specific direction – sound
behind the head is of lower amplitude than in front
 Brain computes difference in amplitude to determine the location of origin
 Useful to determine the location of high-frequency (high pitch) sounds
o Method 2: use difference in time of arrival of sounds between the ears
 Sound needs to travel a longer distance to reach the further ear location
 Brain interprets the difference in arrival time, which is a function of speed of
sound and head size
 Useful for all frequencies, but only for sounds with a clear sudden onset
 Birds sing in gradual increases of amplitude to prevent being localised by
predators
o Method 3: use phase difference between the ears
 Useful primarily to determine the location of low-frequency sounds
 Source of a sound is right in front of face: both ears receive sound waves in
phase
 Sound originates to one side of the head: one ear detects peak, other ear
detects trough; signals detected are 180 degrees out of phase
 Object somewhere in between the front and side of face: everything in
between (eg. 45 / 90 degrees out of phase)
 Vertical axis:
o Cannot make use of difference between ears (unless head is tilted 90 degrees, some
animals do to use horizontal localisation mechanisms in the vertical axis)
o Can use the interference patterns generated by the pinnas to determine the location in
the vertical axis

6.4: Vestibular and somatosensory systems

Vestibular system: conveys information about head rotation

 Vestibular organ: right next to the cochlea in semicircular canals
 Semicircular canal (like cochlea) contains hair cells lining a fluid-filled chamber
o Liquid is called endolymph (like cochlea), contains otoliths (little stones made up of
calcium carbonate)
o Otoliths inside endolymph thought to give the solution bathing the hairs extra weight,
so hairs are displaced more easily with movement
 3 semicircular canals convey information of 3 axis of head rotation
o Shake head (say ‘no’): horizontally oriented canal’s endolymph moves
o Nod head (say ‘yes’): displace endolymph of vertically oriented canal
o Move head such that ear comes closer to the shoulder: endolymph of third canal
moves
 Endolymph moves  hair cells in that canal become active (activated by specific rotation
movements)  signal specific head movement
Somatosentation
 Sensations of the body (touch, deep pressure, cold, warmth, pain, itch, tickles and position
and movement of the joints)
o Each sensation mediated by different receptors
o Burning pain: mediated by receptors in the skin (bare nerve endings / bare axons)
o Receptors also activated by capsaicin (ingredient in chillies that causes warmth,
burning sensation)
o Cold and warm sensations: mediated by thermoreceptor
 Cells also have receptors to menthol (ingredient of mints that make them feel
cool and hot at the same time)
 Sensations all reach the central nervous system through spinal nerves (dermatomes)
o Each dermatome conveys information about specific parts of the body

Eg. Dermatome S1: conveys information about touch in the foot and external segment of the lower
leg; reaches the nervous system through sacral nerve 1

Somatosensory cortex:
Somatosensation reaches anterior parital cortex; signals pass through the thalamus before reaching the
primary somatosensory cortex (like audition and vision)
The somatosensory cortex has somatotopic map of the body – adjacent parts of the cortex process
information of adjacent parts of the body
Similar to tonotopic map of auditory cortex / topographic map of visual cortex

Eg. Most dorsomedial section processes information about the leg, hip, trunk, neck and back of head.
more lateral and ventrally, representation of hand
Further laterally and ventrally: representation of face
Hands, faces eg. have much more cortex devoted to them – sensations here used for important tasks,
such as eating, kissing and manipulating objects
Density of touch receptors here much higher than in other areas (eg. back)
In the visual system: fovea (covers small percentage of visual field) processed by more than half of
the primary visual cortex
We have homunculus in the motor cortex (just anterior to somatosensory cortex)

6.5: Pain
Skin: covered in different types of receptors
 Nociceptors / pain receptors: simple, bare endings that reside in the skin
o Unmyelinated receptors  slow transmission speed
 Two types of nociceptors:
o With large diameter axons: conduct faster and transmit information about sharp pain
o With small diameter axon: conduct slower and transmit information about dull pain
 Two ways to control how fast action potential moves down an axon: whether axon is
myelinated, or size of its diameter

Pain:
 Mild pain triggers release of glutamate in the spinal cord
 Stronger pain: triggers release of glutamate + substance P (neuropeptide; p = powder)
 Pain signals reach the spinal cord  cross over to contralateral side immediately
o Touch signals go up the spine along the ipsilateral side first, only cross over at
midbrain reticular formation
o If left spinal cord damaged, may lose touch sensation on left side, but have intact pain
information on that side. May be unable to feel pain in the contralateral side, but be
able to feel touch there without a problem
 No pain cortex; pain signals segregate along 2 distinct pathways:
o Signals from spinal cord  thalamus projects to primary somatosensory cortex
 Allows us to feel pain and localise it to a particular part of our bodies
o Signals from the spinal cord, reaches the emotional centres of the brain / limbic
system (including amygdala, hippocampus and cingulate cortex)  areas related to
negative emotions associated with pain
 Related to emotional associations of pain

Pain relief systems:

 Opioid system
o Series of mechanisms in the brain to stop prolonged pain
o Opium exerts strong effect by binding to specific receptors in neurons
o Strong pain releases substance P (pain afferent releases substance P on the
postsynaptic neuron)  endorphin producing neuron synapses onto the axon of the
pain afferent and inhibits it (axo-axonal synapse)
o Opioid pain relief takes place primarily in the spinal cord and periaqueductal gray
area of the midbrain
 Cannabinoids: release pain
o Bodies produce endocanaabinoids which normally use the canaabinoid receptors in
our neurons
 Morphine and marijuana highjack already existing pain relief systems and overwhelm them,
since bodies never produce as much of these endogenous neurotransmitters as a single dose of
morphine / marijuana
 Placebo effect: any drug or other procedure with no pharmacological effect, but produces an
effect in the body
o Not a particular chemical system, but some form of unconscious cognitive control
over pain assessments
  Above pain relief systems I have mentioned are related to blocking the emotional response to
pain, but still can feel pain. Other chemicals (eg. anaesthetics) completely block the pain
signals, using other mechanisms

6.6: Chemical senses – taste and smell

Taste:
 Tongues covered in papillae
o Each papilla contains around 20 taste buds
 Taste buds: have small opening (taste pore) allowing solutions that enter
mouth to dissolve in
 Gustatory epithelial cells activated by different chemicals  excite the ganglion cells that
form gustatory nerve
 5 types of gustatory cells distributed through the tongue
o All 5 tastes can be sensed from all parts of the tongue
o 5 cells are those that become activated by salty, sour, bitter, sweet and umami foods
 Taste signals reach brainstem’s nucleus of tractus solitaries  thalamus, hypothalamus or
insula
o From thalamus  primary somatosensory cortex  detect texture of food
o From hypothalamus  areas of limbic system (eg. amygdala and medial prefrontal
cortex)
o Insula (has primary taste cortex): processes information about the taste itself

Smell:
 Olfactory receptor cells (inside nasal airways) contain olfactory cilia (dendrites of olfactory
neurons)
o Cilia contain olfactory receptors
 Humans have several hundred olfactory receptor proteins (not that much since we rely more
heavily on vision and audition)
 Axons of olfactory neurons cross the bone, reach the olfactory bulb (in base of frontal lobe)
 Humans express about one thousand olfactory receptors, but have hundreds of thousands of
olfactory cells
 Olfactory neurons that express the same receptor all across the olfactory epithelium converge
onto the same postsynaptic neurons in olfactory bulb
o So information is not mixed up before reaching the brain
 Summary: Smell signals originate in the nose’s olfactory receptor cells, which have hundreds
of receptor types (one for each smell). This information converges on the olfactory bulb,
located in the base of the frontal lobe
Pre-Lecture 7: Attention, Working Memory and Consciousness

7.1: Cognitive processing and central executive system

Executive functions / executive control / cognitive control:

 Family of mental processes needed to concentrate and pay attention, when going automatic or
relying on instinct / intuition would be ill-advised, insufficient or impossible.
 3 core executive functions which interact to generate higher order executive functions, such
as reasoning, problem solving, planning, etc
o Inhibition / inhibitory control (of distractors)
 Behavioural inhibition (eg. self-control / controlling impulsive decisions)
 Interference control / selective attention: ability to block distracting stimuli
o Working memory
o Cognitive flexibility (set-shifting, mental flexibility, etc)
 Role of frontal lobe in executive functions: appears to be main area involved in cognitive
control or executive functions

7.2: Selective attention: a core function of cognitive processing

Attention: state of the organism that determines how much information can be processed and/or how
fast it can be processed – alertness / arousal
- State changes with sleepiness, fatigue, drugs, and other factors; modulated by ascending
modulatory systems modulate it (norepinephrine, acetylcholine etc)

Selective attention: process of selecting some information (and/or not selecting, or inhibiting some
distracting information) for further processing
- Select small fraction of information, devote a large proportion of our brain processing power
- Rest of information is processed with a small proportion of our brain processing power

Types of selective attention

 Bottom-up / stimulus-driven / exogenous attention
o Stimulus automatically attracted attention (without will or conscious control)
o Attentional signals originate from bottom of brain hierarchy (closer to retina)
 Top-down / internally generated / endogenous attention
o Nothing stood out; pay attention under conscious control – generate command to pay
attention ourselves voluntarily
o Control signals originate in higher areas (eg. frontal lobe)
 Forms:
o Directed to spatial locations, features, orientation, direction of motion or objects
o Overt attention: reflected by action (eg. looking at attended object – eye movement)
o Covert attention: not reflected in an action

Neural mechanisms involved in endogenous selective attention:

 Regions that convey attentional signals to rest of the brain
 Dorsolateral prefrontal cortex conveys attentional signals to posterior visual areas of the brain
 Prefrontal cortex:
 o Neuron in (dorsolateral) prefrontal cortex becomes active only when attention is paid
to items in a specific location of space
 Different neurons active when attention is paid to different parts of space
o Prefrontal neurons are active when attention is directed towards objects inside their
receptive fields
o Inject current (microstimulation) of frontal eye fields (FEF), a prefrontal region 
changes in response properties in V4 (visual area that resemble changes seen when
paying attention to a location in space)
 Can artificially trigger attention to a specific location by activating small area
in prefrontal cortex
o Conclusion: prefrontal cortex is the source of attentional influences over visual areas
 Regions that encode sensory information: Visual cortex
o Visual cortex when attention is directed to specific location:
 Areas V1, V2, V3 active with visual stimulation
 But activation also present when paying attention to specific locations in the
absence of any visual stimulation – there are signals in visual cortex
associated with attention, even in the absence of visual stimulation
o Single-cell level attentional effects:
 Label a neuron’s receptive field (from area MT – motion area), place two
stimuli in it, only fixate on cross
 Pattern A: direction of motion that elicits the weakest response from neuron
 Pattern B: changes every trial; moves in different directions
 Results:
 Movement of pattern B in 0 degree direction  strongest activation
 Movement of pattern B in 180 degree direction (opposite)  smallest
activation
 Movement of pattern A in 180 degree direction  elicits least
response in the cell
 Told to pay attention to pattern B: cell responds more strongly than
in the absence of attention, for all directions of movement
 Told to pay attention to pattern A: cell responds more weakly for
every direction of movement of pattern B
o Conclusion: responses of individual neurons in visual cortex are affected by spatial
attention

7.3: Working memory – key component of cognitive processing

Working memory:
 Capacity to store and manipulate information for a short period of time (vs long-term
memory); essential to numerous cognitive capacities
 Critical for making sense of anything that unfolds over time (eg. understanding written /
spoken language, math, mentally reordering items – to-do lists, translating instructions into
actions…)
o Understanding a phrase: need to briefly remember words at beginning of phrase
 Verbal working memory: maintains verbal objects in memory
 Visuospatial working memory: maintains visual items and their locations in space
Neural mechanisms of working memory:
 Response of neuron in dorsolateral prefrontal cortex in delay saccade task: cell activated as
long as dot appeared in certain area  appears to be maintaining spatial memory information
during delay period
 Whole brain using fMRI: dorsolateral prefrontal cortex and parietal lobe activated by working
memory tasks
o Damage to the prefrontal (not parietal) cortex causes deficits in working memory
 Hence dorsolateral prefrontal cortex is the area involved in maintenance of working memory
(as with selective attention, could be same neural mechanisms)

7.4: Mind/Body problem

Mental phenomena: sensory experiences, thoughts and emotions

 Sensory experiences eg. feeling pain, perceiving redness of red apple
o Phenomenal / qualitative experiences – has ‘feels’
 Intentional states / content-bearing: beliefs, attitudes, desires – not associated with ‘feels’
o Eg. Honesty: tendency to form desires eg. to tell the truth, act in appropriate ways…
 Emotions: anger, joy, sadness, embarrassment, remorse, regret…
 Non-mental phenomena: everything else eg. processes / circulation of blood through arteries

Mind/body problem:
- What is the relationship between mental phenomena?
o Eg. Pain – only sensory event, or can have motivational component to be considered
the mental state pain?
- Relationship between beliefs and desires?
- What is the relationship between minds (mental) and bodies (physical) – phenomena?

Substance dualism (proposed by Rene Descartes in 17th century)

 Thesis that mental and physical substances are fundamentally distinct, exist independent of
each other in this world
 Physicalism: thesis that our world is fundamentally material, consisting only of bits of matter
and complex structure made up of matter, all behaving in accordance with physical laws
o Theories:
 Behaviourism – takes behaviour as constitutive of mentality
 Having a mind a matter of exhibiting, or having a propensity or
capacity to exhibit, appropriate patterns of behaviour
 Identity theory – identification of mental states with the physical processes in
the brain
 No mental events over and above neural processes in the brain
 Functionalism – a state counts as being of a given mental type in virtue of the
functional role it plays within a suitably organized system
 Computationalism: cognition is a form of information processing

7.5: Consciousness

Phenomenal consciousness (qualia)

  Sensory mental events and states have distinctive qualitative characters – sensory qualities of
mental states are “qualia” (raw feels of our experiences)
o Sensory perceptions have qualia – qualitative character
o Eg. feel associated with seeing redness of red, acute sound of a flute, or the soft touch
of hand  know feelings through interpreting them
 Conscious states with such qualitative aspects are called “phenomenal states”  instances of
“phenomenal consciousness” (feels like something to be in this state)
 Some emotions have qualia (eg. anger, envy…)
o Difficult to categorise an emotion as one of resentment, envy, or jealousy based on its
felt qualities alone (unlike sensory perceptions) – need to feel emotion and
understand context
o Felt quality of emotions is coarser than for sensory perceptions, perhaps only negative
and positive feels get attached to beliefs to assign them to a specific emotional
category
 Don’t have qualia:
o Thoughts (eg. beliefs and desires)
o Have unconscious beliefs – associate phenomenal quality with our unaware
phenomenal states?

Access consciousness
- A state is access-conscious if poised for direct control of thought and action
- Conscious  can note content carried by conscious state (eg. it’s raining)  content now
available to various other cognitive functions, like reasoning, decision making, and verbal
reporting (eg. I should bring an umbrella out)
- Cognitive faculties have access to your conscious state (eg. about the rain)

Scientific theories of consciousness:

- Global Workspace Theory: theory of consciousness at cognitive level (vs neural level) – the
mind is a “theatre / global workspace” where conscious states “broadcast” themselves 
representational contents are available to various other cognitive functions and processes
- Multiple Drafts Theory: perceptual-cognitive system constructs multiple pictures (or drafts)
of surroundings, draft that gains prominence at a time (achieves “cerebral celebrity”) is our
conscious state at that time
- Higher Order Thought Theory: consciousness involves some kind of inner awareness of one’s
own mental states. Mental state is a conscious state just in case there is a higher-order
perception (or thought) of it, or perception (or thought) of being in that state

7.6: Consciousness and the mind-body problem

Studying the mind-body problem:

 Explanatory gap: gap between phenomenal consciousness (eg. pain) and the brain (N)
o Every mental state has underlying neural state
o Eg. Pain
o Whenever neural state N occurs  experience pain
o If N does not occur  do not experience pain
o What is it about the neural-biological-physical properties of N that makes it result in
pain, and not another kind of sensory experience?
  Hard problem of consciousness
o Easy problem: understanding relationship between brains and cognitive capacities
o Hard problem: possibly intractable problem of linking phenomenal consciousness and
the brain – how does brain activity lead to the mind?

Key arguments against physicalism – do we understand link between physical and mental?
- Zombie argument: met zombie you (acts exactly like you, but only you have your
consciousness)
- Inverted qualia argument: People in a colour-inverted world behave exactly as we do, though
colour experiences are different

7.7: Disorders of consciousness

Specific disorders of consciousness driven by damage to specific brain sites

 Damage to fusiform face area (FFA)  prosopagnosia (inability to perceive faces, in the
absence of other visual impairments)
 Damage to inferotemporal cortex (IT)  object agnosia (inability to perceive certain objects
excluding faces, in the absence of other visual impairments)
 Damage to the middle temporal area (area MT)  akinetopsia (inability to perceive
movement, in the absence of other visual impairments)
 Damage to the parietal cortex  visuo-spatial neglect (inability to pay attention, and thus
perceive objects in a particular area of space, only if other objects present to compete for
attention)
 Blindsight
o Normally: damage to primary visual cortex (V1 lesions)  completely blind in area
of space covered by damage, rarely – develop blindsight
o Blindsight: ability to detect visual objects, without ability to be consciously aware of
this detection
 Split-brain syndrome
o Damage to the corpus callosum  split-brain syndrome
o Corpus callosum: bundle of nerve fibres / axons that connects the left and the right
hemispheres
o Used to cut the corpus callosum to prevent epileptic seizures from spreading to the
other hemisphere, now only dissect small sections thought to be propagating seizures
o Hence may occur after callosotomy, where left and right hemispheres control
behaviour independent of each other, as if two selves coexisted in the same body

7.8: Neural correlates of consciousness

See visual object  information reaches eyes  LGN  V1  dorsal and ventral visual pathways
 extrastriate visual cortex  prefrontal cortex  plan decision (eg. information motor cortex to
react in actions; information  language areas to respond verbally)

Neural correlates of consciousness (NCCs): minimum neuronal mechanisms jointly sufficient for
any one specific conscious percept
 ‘minimum’: separate neural mechanisms that will not have effect on conscious percept when
removed; left: minimum neuronal mechanism for conscious percept
  ‘jointly’: possible that 2 different neuronal mechanisms lead to same conscious percept (eg.
all combinations of activation of 100 neurons / the thousand in fusiform face area that lead to
face percept
 Not the background conditions necessary for consciousness – factors enabling consciousness
without contributing directly to its content
o Eg. appropriate glucose and oxygen levels, appropriate neuromodulatory milieu and
afferent inputs that ensure adequate cortical excitability

Identifying NCCs:
 Compare neural activity when a particular stimulus (such as a face) is perceived VS neural
activity when stimulus is not perceived
 Keep constant under both circumstances: sensory stimulus and overall state of the participant
 People could perceive stimulus differently (eg. optical illusions)
 Examine possible brain states associated with the different perceptual states
 If there are differences, could be candidate NCCs, because only perceptual state of the subject
changes, since visual stimuli and other conditions of participant kept constant
o Fronto-parietal network activated during visual-motor tasks – contrast perceived
stimuli with invisible stimuli
o Problem: At least part of the neural activity that co-varies with perception of a
particular conscious content reflects processes that precede or follow the experience,
rather than the experience itself
 Bypass problem: No-report Paradigms – do not require report by subject
o Eg. Using eye movements and pupil dilation (correlate tightly with conscious reports
of perceptual tasks)  determine what subject is perceiving without asking
o No-report paradigms identify a more restricted content-specific NCC, which typically
includes posterior cortical areas but not the prefrontal cortex
 Summary: paradigms that require behavioural report tend to find fronto-parietal activation;
no-report paradigms tend to only find activation in posterior cortical areas
Pre-Lecture 8: Decision Making

8.1: Background on movement

Muscles:
 3 types of muscle:
o Smooth muscle (intestines and other organs): long, thin cells; under control of
autonomic nervous system – not under conscious control
o Skeletal / striated muscles (eg. in arms and legs): long cylindrical fibres with stripes;
can be controlled by central nervous system, and help control movement in relation to
the environment
o Cardiac muscle (in heart): fibres that fuse at various points
 Cardiac muscles contract together, not independently due to fusions
 Each muscle is composed of many muscle fibres
o Each fibre receives information from only one axon; one axon may innervate more
than one muscle fibre
 Some muscles have ratios of about one axon per three muscle fibres (eg. eye muscles), others
can have ratios as large as one axon per hundred fibres (eg. biceps)
o Hence eye can move more precisely than bicep

Transmission of information to muscles

 Axons transmit through synapses
o Neuron to muscle synapse: neuromuscular junction)
 Skeletal muscles: every axon releases acetylcholine (excites muscle to contract)
 Muscles only contract, relaxes when receives no message to contract
 At neuromuscular junction:
o Action potential comes down through axon of the motor neuron (myelin sheath that
insulates it)  reaches the axon terminal  depolarisation  opening of voltage-
gated Ca++ channels  Ca++ flows into cell (attracted by lower concentration
inside, and negative membrane potential)  vesicles filled with acetylcholine fuse 
released to synaptic cleft
o Acetylcholine binds to ligand-gated channel selective to positive charges
o Channel opens  Na+ flows into cell, K+ flows out  membrane depolarises
 Like photoreceptors in the dark
o  Voltage-gated Na+ channels in vicinity of synapse open  action potential
generated in the muscle fibre  contraction of muscle
 Summary: muscles contracted in response to activation of a motor neuron which synapses
onto the muscle fibres through the neuromuscular junction, which uses acetylcholine to evoke
a muscle-fibre action potential

Movement control in the absence of conscious intention

 Reflex actions; mainly through proprioceptive system
 Proprioceptors:
o Muscle spindle: receptor parallel to muscle; responds to a stretch
 Muscle spindle stretched  sensory nerve sends message to motor neuron in
the spinal cord  message sent back to muscles surrounding the spindle 
contraction
  Reflex provides for negative feedback – when a muscle and its spindle are
stretched, the spindle message  muscle contraction that opposes the stretch
o Golgi tendon organ: in tendons at opposite ends of a muscle; act as brake against
excessively vigorous contractions
 Some muscles so strong they could damage themselves if too many fibres
contracted at once
 Detect tension that results during a muscle contraction  impulses travel to
the spinal cord  excite interneurons inhibiting the motor neurons
 Summary: vigorous muscle contraction inhibits further contraction by
activating the Golgi tendon organs
 Proprioceptors also provide our brain with information about your body’s position, can be
used for conscious adjustments of movements

8.2: Brain mechanisms of movement control

Primary motor cortex: located in posterior aspect of frontal lobe, just anterior to the central sulcus
(separates frontal and parietal lobes)
 Motor pathways:
o Lateral corticospinal tract
 Controls precise movements of extremities (eg. hands, fingers and feet)
 Axons originate from neurons in the primary motor cortex (area M1) and
from red nucleus (large nucleus in midbrain) – upper motor neurons
 Distinguished from lower motor neurons in the spinal cord
 Large axonal tract generated by these neurons moves towards their final
targets in the spinal cord by bundling up at the level of the medulla in the
pyramids
 Tract crosses to contralateral side  synapse onto lower motor neurons that
control muscles in the opposite side of the body
o Medial corticospinal tract
 Controls muscles of the neck, shoulders, and trunk. Movements eg. walking,
sitting
 Axons originate from neurons in multiple cortical areas (eg. primary motor
cortex, premotor cortex, temporal lobe)
 Axons also originate from subcortical structures (eg. tectum, reticular
formation, vestibular nuclei in midbrain)
 Axons go to both sides of the spinal cord

Other areas important in modulating movement control: cerebellum and basal ganglia
 Cerebellum:
o Damage to area: trouble with rapid movements requiring aim, timing and alternation
of movements (eg. tapping a rhythm)
o Recently, in modulating other non-motor processes (eg. keeping track of time)
 Basal ganglia:
o Primarily composed of dorsal striatum, ventral striatum and globus pallidus
o Unlike thalamic nuclei, which receive inputs from the periphery and project to cortex,
for example, to transmit visual or auditory information to the cortex, input to the
caudate and putamen comes mostly from the cerebral cortex
 o Output from the caudate and putamen  globus pallidus  thalamus and midbrain
 cerebral cortex (especially motor areas and prefrontal cortex)
 Cortico-basal ganglia loop – cortical information passes through the basal
ganglia, and goes back to cortex
 Contrast with thalamic nuclei: receive inputs from periphery  project to
cortex (eg. to transmit visual or auditory information to cortex); input to
caudate and putamen comes mostly from cerebral cortex
o Basal ganglia inhibit movements
 Damage  decreased inhibition  involuntary, jerky movements (eg.
Huntington’s disease)

8.3: Movement preparation

Motor cortex is important for the execution of movements, but not planning

Cortical areas involved in movement planning:

 Posterior parietal cortex: one of the first areas to become active during movement planning
o Microstimulation here  people report intention to move (eg. left hand)
o Stronger stimulation  people report they believe they moved, even though they
haven’t (in absence of visual feedback)
 Premotor cortex (anterior to primary motor cortex) most active immediately before movement
o Neurons in this area have sustained activation to specific movements, even if the plan
precedes the execution of the movement by many seconds
o Eg. Planning to raise right hand:
 Cells in premotor cortex that are active: those with selectivity to right arm, to
raising arm
 Inactive cells: with selectivity to left arm, to lowering arm
 Supplementary motor cortex (SMA): dorsal to the premotor cortex; involved in motor
planning
o Involved in motor imagery, bimanual motor tasks and sequential motor action
 Eg. Typing, playing complex sequence in a piano
 Playing piano activates SMA and primary motor cortex
 Imagining playing piano without actual movements only engages SMA
o SMA neurons also important in initiating actions based on self-generated time
estimates, important for complex actions

Mirror neurons (in premotor cortex):

- Active both during preparation for a movement and while watching someone else perform the
same or similar movement
- First identified in premotor cortex
- Hypothesised to be basis of animals’ social behaviour

Conscious decisions:
 Where or when in brain pathway involved in movement planning did we make a conscious
decision to move?
 Do we consciously decide to do something, and then do it?
  Study appeared to suggest that brain activity responsible for movement begins before
conscious decision
o Conscious decision does not cause your action
o Become conscious of the decision after the process leading to action has already been
under way for about 300ms.
 Another study found frontal and parietal cortical areas showed activity specific to left or right
movements 7 to 10 seconds before response
o Activity reflected the history of prior selections by the subject
o Subjects don’t behave fully randomly in responses, activity wasn’t really predictive
of decision
 Summary: conscious decision making may reflect awareness of ongoing unconscious decision
processes in the brain

8.4: Value-based decision making

Value-based decision making / economic decision making: involves selection action based on value
assigned to their outcomes

Considerations:
- Hedonic factors (eg. pleasure / displeasure of taste of cravings)
- Homeostatic factors (eg. hunger level)
- Series of cognitive factors (eg. health considerations, value assigned to eating healthy to live
longer)
o Social considerations (eg. gaining or losing weight to look good)
o Moral considerations (eg. vegan to prevent animal suffering)

Factors modifying value of rewards:

- Subjective values of different options compared to determine which action to take
- Subjective value of rewards associated with different actions are reduced / discounted by
o Probability of attaining them (eg. success rate)
o Delay in attaining them – temporal discounting
o Effort involved in attaining them

Neuroeconomics: field seeking to uncover neural mechanisms of economic decision-making

Medial prefrontal cortex key region involved in decision making (once, also posterior cingulate
cortex?)

8.5: Movement disorders

Pure movement disorders: spinal / peripheral nerve damage

- Patients cannot move, but cognition intact

In the midbrain:
- Cerebral peduncles: carries motor fibres from the motor cortex to the spinal cord
- Substantia nigra: involved in visual reflexes; receives direct input from retina
o Produces dopamine in brain; projects primarily to basal ganglia
- Red nucleus: motor nucleus; controls movements together with motor cortex
 - Colliculi

Parkinson’s disease:
 Degeneration of dopaminergic neurons here  motor symptoms of Parkinson’s disease
 Characterised by rigidity, muscle tremors, slow movements, and difficulty initiating physical
and mental activity
o Not paralysed / weak; have difficulty with spontaneous movements in the absence of
stimuli to guide their actions
 Average over 45 loses substantia nigra neurons at almost 1% a year, but mostly have enough
so never show symptoms
o Once 20-30% of neurons degenerate, Parkinson’s symptoms begin, become more
severe as cell loss continues
 Genes can cause early-onset Parkinson’s disease (condition develops before 50)
 Environmental influences may cause late-onset
o Eg. Mistake in production of MPPP  produced MPTP  paralysed when consumed
(found MPTP destroyed all dopaminergic neurons); later found many hazardous
chemicals in herbicides and pesticides resemble MPTP
 Most common treatment: L-dopa / levodopa (precursor for dopamine)
o Used rather than dopamine since can cross blood-brain barrier (barrier preventing
certain chemicals from crossing blood vessels of the brain) while dopamine cannot
o Problems of L-dopa:
 Ineffective for some patients
 Does not prevent the further loss of neurons – over time still deteriorates
 Series of unpleasant side-effects (eg. nausea, sleep problems, hallucinations
and delusions)
 Alternative treatments developed
o Drugs that prevent further neuronal death
o Stem-cell therapy: replenish dead cells
o Deep brain stimulation: increase release of dopamine
 Still doesn’t prevent further degeneration of cells

Huntington’s disease
 Neurological disorder characterised by motor and cognitive deficits (eg. tremors – interfere
with walking, speech, voluntary movements; ability to learn and improve new movements is
severely limited)
 Patients may develop depression, anxiety, hallucinations and delusions, memory impairments,
poor judgement, drug abuse and sexual disorders
 Disorder associated with gradual, extensive brain damage, primarily in the basal ganglia and
cortex
 Severe damage to the caudate, putamen and globus pallidus; ventricle is expanded
 Has a clear genetic cause, can get genetic test to assess probability of getting the disease
 No treatment exists that cures or prevents the condition
Learning and Memory

Types of Memory

Learning – the activity or process of gaining knowledge or skill by studying, practicing, being taught
or experiencing something

Memory – the things learned and kept in the mind, can be acquired and also lost

Types of memory
- Sensory
o < 1 second
o Brief trace of a sensory stimulus in your brain
- Short-term (working memory)
o < 1 minute
o Memory of events that just occurred
 Limited capacity
 Fades quickly without rehearsal or attention – requires active maintenance in
your cognitive
 Once is forgotten, it is lost – it was an activity trace
 Can in theory maintain short term memory for a full day if y ou keep thinking
about it

- Long-term
o Life-time
o Memories that occurred further back
 Large capacity
 Does not fade in the absence of attention
 You may remember something you thought you had forgotten (with a hint)
 Cannot be distracted into forgetting this

All information enters the short term memory. It MAY then be consolidated into long-term memory

Long Term memory

- Explicit memory (conscious – can declare/say)
o Declarative memory (facts, events) – same as explicit memory
 Episodic memory (events, experiences)
 Snapshots in time – memories of things that happened at a specific
point in time
 In a couple of days, you might forget it
 Semantic memory (facts, concepts)
 Eg who is the pm of Singapore? Lee hsien long
 Not associated with a specific moment in time
 Initially encoded as episodic memories but as time passes, you forget
how you learned the fact and it becomes semantic memory
- Implicit memory (unconscious – can’t state or declare, you just do it)
 o Procedural memory (skills, tasks)
o Priming – an implicit memory effect in which exposure to one stimulus (eg
perceptual pattern) influences the response to another stimulus
 Eg if I show u 3 pics of bread then so_p u would prob say soup

Scientific Study of Memory

Types of conditioning
- Classical conditioning (pavlovian conditioning)

o
o Converting an unconditioned stimulus to a conditioned stimulus, to create a
conditioned response
o Involves placing a neutral signal before a reflex
o Focuses on involuntary, automatic behaviours (reflexes)
o First described by ivan pavlov, a russion physiologist
o Eg
 if there is an attractive model in a car commercial, men rate the car as being
faster and more appealing
 aversion therapy – condition people to associate smth they like but is harmful
with something they hate to force them to give it up

- Operant conditioning (instrumental conditioning)

 o
o Reward and punishment conditioning
o Involves applying a reward or punishment after a behaviour
o Focuses on strengthening or weakening voluntary behaviours
o First described by b.f skinner, an American psychologist
o Eg
 if you study and do well in your midterm, itll reinforce your studying
behaviour and you’ll get an a in ur final exam
 if a baby receives an electric shock after touching a plug, she’ll learn not to
touch the plug in the future

Brain areas involved in memory

Engram – the physical representation of what has been learned

- pavlov reasoned that the physical representation of classical conditioning must involve new
connections in the brain linking the conditioned stimuli and the conditioned response
o connection strengths between neurons shape and store information and memories
o same principle that applies today in artificial intelligence
- karl s Lashley decided to test this hypothesis in 1930 by doing cuts all around the brain trying
to break conditioned behaviour
o trained rats to salivate to a bell, then did little cuts all across the brain
 no memories were lost no matter where he cut
 concluded that memory did not depend on connections in the brain
o if its not connections in the brain, he hypothesized that certain brain regions may
contain the memories
 removed different parts of the brain after learning
  his result was that memory loss was a function of the amount of tissue
removed
 conclusion: memory does not rely on a single area, but rather on all areas
equally (equipotentiality)
o now, we know that his conclusions are not valid because of flawed experimental
methods and theoretical assumptions
 for the expt where he removed parts of the brain, he failed to realise that
performance of the task did not only involve intact memory, but also sensory,
motor and decision making circuits. Damage to any of these results in
decreased performance (so there are multiple memory mechanisms)
 Eg he took the animals not moving as a sign that they couldn’t rmb,
but it could be bcos their motor cortex was cut so they physically
couldn’t
 He also assumed that cortex was the only place to look and that all memories
have the same mechanisms (there are subcortical memory mechanisms)
 Both assumptions are flawed, as we know today.

neural basis of classical conditioning (implicit memory) - Eye-blink conditioning studying cerebellar
function

-
- Conditions people to blink after the sound, because they were conditioned to by pairing the
sound with the air puff -> implicit learning that happens in humans and other animals

-
o Each of these are the cell body and axon of a neuron
o Sensory neurons in the cochlea sense the tone, then they transmit this information to
another neuron, which synapses onto another neuron etc until we reach the motor
neuron that generates the blinking of the eye
 o If connections between neurons are the sites of memory consolidation, should be able
to identify where in this circuit this occurs

 Eg this site of engram is between d&e

 When you strengthen/weaken the synapses, the sensory input will be
transformed from the sound to a blink
 Blocking any of the connections before the D/E connection or damaging
them would lead to no learning and no conditioned response
 Sensory input has no way of reaching memory / motor output 
won’t blink
 Blocking any of the connections after E would lead to no conditioned
response since the blinking movement is blocked, but it could still lead to
learning since these synapses will be modified (just that this learning will not
be reflected by the movement)
 A: cell body axons from neuron
 Air puff paired with sound (unconditioned stimulus)  blink (unconditioned
response)
 Sound (conditioned stimulus)  blink (conditioned response)
- Implicit memory: cerebellum and basal ganglia

o done in rabbits
o lateral interpositus nucleus of cerebellum is D
o sound signals (through a series of pathways) reach cerebellar nucleus, lateral
interpositus nucleus of the cerebellum (LIP)
 LIP receives auditory inputs
o LIP projects to the red nucleus of midbrain (green arrow) this is E
o Red nucleus projects to the sixth cranial nerve (F) that controls blinking
o Basically is LIP -> red nucleus -> sixth cranial nerve
o What researchers did

 Blocked learning through blocking LIP neurons

 Eg inject GABA to inhibit
 Cool down nucleus so it doesn’t fire action potentials
 The signal never reaches the rest of the brain -> no response, no
learning -> no blinking
 Blocked the red nucleus
 No response, Normal learning
 Eg u block the red nucleus then u do the air puff without the sound so
there will be no blinking
 But when u remove the block later, the animal blinks when the sound
is played
 Allowed them to identify that the synapse from LIP to red nucleus is where
learning takes place (engram) – plasticity in synapses between LIP and red
nucleus was engram of memory
 Memory formation and location of learning is the same
 Most other types of learning are very distributed, not usually the case
where learning is specifically located in one region
o Cerebellum is involved in classical conditioning learning (at least in eye blink
conditioning)
o If the delay between the conditioned stimulus and unconditioned stimulus is longer
than 2 seconds, the cerebellum recruits another structure for learning: the basal
ganglia
- Basal ganglia (important for implicit information)

o Basal ganglia is mostly frontal lobe, which is the motor cortex and the prefrontal
cortex – motor controls and cognitive controls
 Frontal loops – frontal cortex: motor cortex + prefrontal cortex  motor and
cognitive controls in basal ganglia
o Weather prediction task


Participants quickly figure out that 1 or 2 of the cards are informative, and
start following them (eg most of the time triangles appear it will be sunny)
which leds to a 62.5% accuracy in prediction
 As time goes, they start increasing their performance as they include info
from other cards into their decisions. They may not be aware of this, but it
happens anyway. If you ask them why they respond in certain ways, they
may say they have a ‘hunch’
 Not an explicit memory since they cannot tell you what they are
doing
 People with parkinsons disease who have impairments of the basal ganglia
have no problem forming the initial rule (if triangles then rain) but are unable
to improve beyond that
 basal ganglia is in required for this additional incorporation of
information
- Hippocampus (involved in explicit memory)
o middle temporal lobe of the brain
 tip end of the cortical surface
  normally considered sub-cortical but can be thought of as an extension of the
cortex (lateral geniculate nucleus LGN)
 Specialisation (deep end of cortical surface)  goes and comes around
middle of temporal lobe
o effect of hippocampus removal
 the famous case of patient H.M
 to prevent epileptic attacks, a neurosurgeon removed bilaterally
H.M.’s hippocampus and parahippocampal areas (areas adjacent to
the hippocampus)
 Here in many cases is the locus that initiates seizures (which don’t go
away with drugs)
 case study
o he remembers the emotions associated with the experiences,
but not the experiences themselves
 effects shown by the patient (mostly explicit memory is affected)
 anterograde amnesia
o inability to form memories for events that happened after
brain damage
o information is in his brain, just unable to convert it to long-
term memory
o some positive/negative associations can be developed
 retrograde amnesia
o loss of memory for events that occurred before brain damage
o more severe for events that occurred closer to brain damage.
Eg amnesiac patients can remember their childhood homes
but not their home from 2 years ago.
o More severe for episodic memory than semantic memory
 Intact working memory
o If left undistracted, h.m. can remember names, numbers etc
 Better implicit than explicit memory
o Not surprising since cerebellum and basal ganglia are
undamaged
 Intact procedural memory
o A form of implicit memory
o Not surprising since cerebellum and basal ganglia are
undamaged
o Role of hippocampus in spatial memory
 Studies (mostly involving rodents)
 Morris water maze
o There is a rodent in a pool of water that is trying to find a
platform so it doesn’t drown. In the middle of the pool is a
platform that it can stand on. At first it cant find it, then the
researcher helps it and eventually it learns that the platform
is safe. After a few tries, the rodent finds the platform
immediately even though it is hidden. It uses spatial cues like
 the lighting, the positioning etc to figure out where it is in
relation to the platform.
o

 Rat’s movement through the water on each trial

o Learning is impaired in rats with hippocampus damage
 Random foraging: spatial selectivity

o Recording done from one neuron in a rat’s brain

o Rat is placed in a box, researcher’s scattered treats so that the
rats can find them
o Sound + blue dot whenever action potential happens in the
hippocampal nerve being observed
o Neuron fired whenever the rat was in that particular area,
other neurons would have different active areas
o Between all the hippocampal cells, the entire spatial area
would be covered

o
 Place cells repond only in one location
  Grid cells have an organized arrangement of place
fields that form a lattice spanning the whole
environment
 Different places  different place fields

 2014 Nobel prize in physiology or medicine was

given to dr john m o keefe, dr may britt moser and dr
edvart l moser for their discoveries of nerve cells in
the brain that enable a sense of place and navigation
 Types of selectivity in hippocampal formation

 Link between navigation and memory

 Cells are harder to identify in monkeys and humans, but there has
been decent evidence to prove their existence


o Fmri done to assess grid cells

o If humans travel in the aligned segments, their cell activity
would be very high as they encounter many fields with high
activity
o Grid cells have fixed angles
o If subject moves in the misaligned fields, they will not
encounter as many grid fields
 o Entorienal cortex?? (EC) showed activity that was predicted
by those alignements in humans -> humans have grid cells in
their EC
 Navigation is not just spatial, it can be social, knowledge structures -
> hippocampus allows encoding of information about cognitive
maps, not just spatial maps
o Eg social hierarchies in an environment, or similarities of
concepts
 Don’t really know the structure the concepts are
stored in
- Other regions involving memory
o Parietal cortex
 Cortical areas are specialized in different ways in memory processing/storing
 Parietal damage can lead to the inability to link one memory to another
o Anterior temporal lobe
 Damage can lead to semantic dementia: selective forgetting of what objects
are (eg what is a zebra)
o Medial prefrontal lobe
 Damage can lead to deficits learning about rewards and punishments
o Amygdala (not in cortex)
 Damage can lead to deficit in fear memories

Cellular Mechanisms of Memory Formation

Donald O Hebb and Hebbian Synapses
- Proposed that an axon that has successfully stimulated another cell in the past becomes even
more successful in the future
- ‘cells that fire together, wire together’
o Not entirely accurate as hebb required causal interactions, not just co-firing)

Single cell mechanisms of invertebrate behaviour change

- Aplysia (large sea slug)
o Why use this?
 Used bcos invertebrates are much simpler than vertebrates, so easier to
understand their nervous systems
 Vertebrates share a common ancestor, so we might discover mechanisms that
apply to vertebrates including humans
 They do have similar processes to humans, not rly cognition tho
o Study
 Gill withdrawal reflex
 Poke their siphon and the gill will withdraw a little
 Tail shock - Electrocute the tail, and the gill will withdraw a lot
 Sensitization – ‘after electrocution, even merely touching will evoke
a huge gill withdrawal response
o Animal overreacts to the same stimulus
o Results
  Sensitization – after a strong stimulus, a subsequent mild stimulus evokes a
strong reflex
 Habituation – after a mild stimulus, a subsequent mild stimulus evokes a
weaker reflex
- Mechanisms
o Habituation

 From the syphon, there are sensory neurons that innervate the syphon
 These sensory neurons synapse onto a motor neuron which then activates the
muscle that controls the gill retraction
 Two neurons involved in controlling this reflex
 The number of action potentials from the sensory neuron are not changing as
habituation proceeds
 There is a decrease in the release of neurotransmitters at the synapse as the
cell is repeatedly activated
 This could be because you are running out of synaptic vesicles and
cannot refill them fast enough
 Many possible reasons for this to happen
 End result is: for every action potential that happens in the sensory
neuron, there will be less vesicles that are released -> motor neuron is
activated less -> habituation occurs and muscle contracts less -> gill
is retracted less
o Sensitization

 Involves a serotonergic neuron

 Sensory neuron not only conveys information to the motor neuron, also sends
a side branch to synapse onto a serotonergic neuron -> serotonergic neuron
sends its axon towards where the interaction between sensory and motor
neurons occurs
 With an electric shock, higher activation of the sensory system -> leads to
activation (or overactivation) of serotonergic neuron (doesn’t happen
normally if you only touch the syphon) -> releases a cloud of
neurotransmitter serotonin -> blocks potassium channels in the membranes of
these cells (leak channels that are maintaining the voltage of the neurons in a
hyperpolarised state)-> membrane is slightly more depolarized and the
voltage will increase slightly -> presynaptic neuron is more likely to activate
and release more neurotransmitters for longer than usual, increasing the
depolarization
 Because of this, whenever sensory neuron is active in the presence of
serotonin, there will be a larger response from the motor neuron, which is
sensitization
o This is all short-term changes before it goes back to normal. If either happens over a
long term, it will become a long-term change in the system.
  This process of transforming short-term changes into long-term changes
requires changes in the synthesis of new proteins and expressions of genes
etc
 Short-term plasticity (sensitization and habituation) that can get transformed
into a long-term plasticity
o Both lead to changes in the motor neuron, not the sensory neuron

Synaptic Plasticity
- Long-term potentiation (LTP) – increased strength of an individual synapse for a period of up
to weeks
o Can have many different mechanisms
- Long-term depression (LTD) – decreased strength of an individual synapse for a period of up
to weeks
- Both happen in many neurons in the brain, but are particularly strong in hippocampal cells
- Mechanisms

o Patch-clamp recording of a neuron (measure sub-threshold voltages)

 Cell x receives inputs from cells 1, 2 and 3
 This is plotting the activation/depolarization/voltage change of cell x, as
driven by the activation of one action potential in cell 2
 One action potential comes from cell 2 to cell x, and it will evoke a certain
activity/level of depolarization.
 Before long term potentiation, there is some level of depolarization
 The researcher then activates cell 1 and 2 simultaneously for 5 minutes ->
depolarization is higher
 Then, cell 1 will stop being activated and only activate cell 2.
 Increase compared to baseline of the depolarization evoked just by a
single action potential in cell 2
 This change is what is referred to as LTP
 Researchers kept going for 70 minutes and it was still higher than
before the sensitization -> long term effect
o Biochemical mechanism of NMDA-dependent LTP

 Synapse between cell 2 and cell x is a glutamatergic synapse

 Cell x’s dendrites contain two types of glutamatergic synapses that are
ionotropic (ions can pass through freely)
 AMPA receptors
o Primarily permeable to sodium
 NMDA receptors
o Permeable to sodium and calcium
 When one synapse comes and only cell 2 is active, glutamate comes out and
binds to both AMPA and NMDA receptors
 AMPA receptors open and allow sodium to pass
 NMDA receptors have a pore where sodium and calcium can go in, it
also tracks magnesium (huge double positive ion) -> magnesium
blocks the pore and does not allow anything to enter -> magnesium is
attracted ot the inside of the cell since it is negative and magnesium
is positive + it is more concentrated outside the cell than inside
(electrochemical gradient is strongly driving magnesium to enter the
cell) -> cannot enter since its too large so it just blocks the pore,
rendering NMDA useless
 LTP: Add more AMPA receptors to post synaptic cell, have more synaptic
vesicles in presynaptic cell, generate additional synapses between two
neurons
 Now that cells 1 and 2 are co-active, this is when learning and
potentiation of cell 2 synapse occurs
 When 2 synapses are simultaneously active, and that are adjacent to
each other, you open AMPA receptors in both synapses which leads
to higher depolarization -> inside of the cell becomes more positive -
> magnesium is less attracted, and can now be displaced -> NMDA
pore becomes permeable to sodium and calcium
 Calcium is now allowed to enter the cell, which triggers a series of
biochemical events that leads to the expression of genes that increase
the number of AMPA receptors in the synapse -> stronger synapse ->
same release of neurotransmitters will lead to more depolarization
because there are more receptors
 Drugs that block NMDA receptors prevent establishment of LTP but
not its maintenance
o This is bcos the maintenance of LTP is driven by the
increased number of AMPA receptors, so blocking an
NMDA does not erase any of your acquired memories. It just
prevents calcium from entering so you cannot strengthen it
even more
o Biochemical mechanism of LTP


 LTP can increase synaptic strength by increasing receptors in the
post synaptic cell, or by increasing synaptic vesicles in the pre-
synaptic cell
o Can change the amount of vesciles, and the amount of
neurotransmitters within each vesicle


 LTP can be due to the formation of new synapses
Lecture 9: Sleep

Body Rhythms
 Eg. Sleep
 Exogenous factors: influence cycles
 Endogenous cycles: internally generated by our body
o Circannual cycles: yearly cycles
o Circadian cycles: daily cycles (eg. sleeping, eating, mood, body temperature,
urination, secretion of hormones etc)
 Persist even in the absence of external cues
 Change with age (eg. sleeping / waking timing)
 Adjusted by exogenous factors (internal cycles readjusted daily to stay in
phase with the world)
 Hence not born with perfectly synchronised internal clock
 Failure in evolution
 Length of day depends on seasons and geographical location
 Some people do have perfect synchronisation
 Sometimes external factors not fast enough at changing circadian cycles
(speed of change of environment > speed of change of internal rhythms being
affected) eg. jet lag

Neural Mechanisms of Body Rhythms

 Suprachiasmatic nucleus (in hypothalamus): lies just above optic chiasm
o Photoreceptive retinal ganglion cells project (send inputs) to it
o Has photo pigments in ganglion cells
 Cells more sensitive to short-wavelength (blue) light
 Computers and cell phones emit high percentage of short-wavelength
light  harder to fall asleep (adjusting circadian rhythms with cues
not supposed to adjust it eg. looking at screen at night – brain fooled
into thinking it’s daytime, and should be awake)
o Classes of photoreceptors in our bodies: rods, cones, photoreceptive ganglion cells
o Other functions of photosensitive RGCs other than regulating circadian rhythms
 Regulating pupil size
 Can coordinate signals of luminosity in whole retina to control whole
contraction of pupil
 Very slow dynamics of response – respond / adjust to light slowly as
compared to cones for perception
 Takes in in terms of very tiny receptive fields
 Photos enter eye through retina  optic nerve  project to
hypothalamus (SCN)  fibres from photoreceptors innervate SCN
neurons  activity of cells in SCN fluctuate depending on
luminosity in environment
o Genetic “clocks” inside SCN neurons – molecular mechanisms controlling circadian
rhythm
 mRNA of PER and Tim low at waking  peak in sleep  decrease during
sleep (opposite is true for their proteins)
 DNA (gene) generates mRNA, mRNA generates protein
  Proteins PER and TIM promote sleep, inhibit genes that produce PER and
TIM (negative feedback)
 Takes time for translation: increased protein  increased inhibition of
mRNA production  decreased mRNA  decreased protein (cycle)
 Light activates enzyme that breaks down TIM protein, adjusting the cycle
 Light generates activity in retinal ganglion cells (photoreceptors),
input  SCN; activates enzyme TIM
 Break down increases  inhibit less production of mRNA  sleep later
(mechanism that allows cycles and modulatory systems??)
 Mutations in PER and TIM genes causes sleep problems and depression
o SCN cells isolated from body continue to produce circadian rhythm; damage to other
parts disrupt circadian rhythm (not source of it)
 Melatonin
o SCN projects directly to pineal gland (not a nucleus) – produces hormones,
neurotransmitters released into blood and circulate in body
o Melatonin levels increase at night; pills taken 2 hours before desired bedtime relief
jetlag

Stages of Sleep
 Sleep and other interruptions of consciousness:
o Sleep – state the brain actively produces (active process); characterised by decreased
response to stimuli
o Coma – extended period of unconsciousness caused by head trauma, stroke or
disease; characterised by low brain activity, low response to stimuli, no purposeful
movements
o Vegetative state – alternates between periods of sleep and low arousal; characterised
by low response to stimuli and no purposeful movements
o Minimally conscious state – like vegetative state, but with occasional brief periods of
purposeful actions and limited amount of speech comprehension
o Brain death – no brain activity
 Stages of sleep: measured by polysomnography (combination of EEG and eye-movement
records (ENG) through electrodes
o Fourier Decomposition: lower frequency, higher amplitude, higher power (greater
distance from peak to trough)??
o Frequency bands:
 Beta waves 15-30 Hz
 Alpha waves 9-14 Hz
 Theta waves 4-8 Hz
 Delta waves 1-3 Hz
o Relaxed, awake: high alpha waves – alpha waves are characteristic of relaxation but
not all of wakefulness
o Non-REM sleep:
 Stage 1 sleep: Irregular, low-voltage waves (here can still respond, drifting
off to sleep)
 Stage 2 sleep: Large, low frequency oscillations Sleep spindles – interactions
between thalamus and cortex (12-14 Hz); K-complex (inhibition of neuronal
firing in cortex) (here cannot respond)
  Stage 3 sleep
 Stage 4 sleep: Slow wave sleep (SWS) includes large waves in delta range
(0.5 – 4 Hz)
 Large delta waves in EEG signal in stages 3 and 4 show
synchronised activity for brain processing – so cells are active and
quiet at the same time (doesn’t mean there’s a lot of activity due to
dreams / little activity due to deep sleep)
 Deep sleep (stages 3 and 4) dominate early in the night
o REM Sleep:
 Low-voltage waves (Similar to stage 1 sleep) and rapid eye movements –
indicate increased neuronal activity  REM sleep is light
 Postural muscles more relaxed than in other sleep stages  REM sleep is
deep
 Sleep state with similarities to awake state  paradoxical
 REM sleep dominates towards morning
 Dreams more common during REM (but also happen during non-REM)

Brain Mechanisms
 Brain mechanisms of wakefulness
o Basal forebrain:
 Releases acetylcholine (increases arousal) during wake and REM sleep
o Hypothalamus:
 Releases histamine and orexin
 Widespread excitatory effects (antihistamines produce sleepiness)
 Orexin keeps us awake
 Narcolepsy caused by lack of orexin
o Locus coeruleus:
 Releases norepinephrine through cortex (tiny area, huge influence)
 Increases wakefulness due to emotional arousal (dormant during sleep)
o Reticular formation and pontomesencephalon:
 Release acetylcholine and glutamate
 Project to hypothalamus, thalamus and basal forebrain
 Maintains arousal during wakefulness
 Brain mechanisms of sleep
o Basal forebrain:
 Releases GABA (main inhibitory neurotransmitter – essential for sleep)
o Dolphins: can keep one hemisphere awake while other is sleeping to control
swimming and breathing
o Local sleep:
 When awake parts of brain may go to sleep (tired / sleep deprived)
 When asleep parts of your brain may wake up (rested after some sleep)
 From frontal and parietal electrodes: brain goes into microsleep for half a
second (silent)
o Selective sleep deprivation
 Didn’t enter stage 3 or 4 of non-REM sleep  wake up tired after whole
night feeling tired
  Didn’t enter REM sleep  feel rested; but if repeated over many nights,
could start hallucinating during waking time

Sleep Disorders
 Insomnia – inadequate sleep
 Sleep apnea: sleep disorder characterised by inability to breathe while sleeping for a
prolonged period of time
o Consequences: sleepiness, impaired attention, depression, heart problems
o Causes: genetic, hormones, old age, obesity, deterioration of brain mechanisms
controlling breathing
 Narcolepsy: neurological disorder due to loss of neurons producing orexin (in hypothalamus)
o Main symptoms:
 Attacks of sleepiness during the day
 Occasional cataplexy: attack of muscle weakness while person remains
awake; often triggered by strong emotions eg. anger / great excitement
 Sleep paralysis: inability to move while falling asleep / waking up; could also
be experienced by healthy individuals
 Hypnagogic hallucinations: dreamlike experiences that person has trouble
distinguishing from reality
o No good treatments available
 Sleepwalking: parts of brain awake while some asleep
o Causes not well understood
o Most common during sleepless SWS (not during REM, since most large muscles
completely paralysed)

Why sleep? Why REM? Why dreams?

 Sleep is an active process – we evolved mechanisms that force us to sleep
 Don’t sleep:
o More vulnerable to mental illness
o Less attentional capacity  poor performance in schools and more accidents
o Poor memory consolidation
 Sleep:
o To save energy
o Animals awake when it’s more efficient (eat, avoid predators, mate…)
o Some deep-sea fish never sleep – no difference between light and day
 Consolidation of memories during sleep:
o Forward and reverse replay occur during sleep; replay also occurs during awake
period (resting – to reinforce?)
o All synapses downscaled (decrease in size) such that
 Memories are maintained
 Brain connections do not saturate
 If not, fully connected brain – cannot learn anymore
 Occurs primarily in weak synapses; strong synapses stay – so memories not
broken down (remaining – noise; not strong enough to encode a memory, so
other memories can come in)
 Sleep drives metabolite clearance
 REM sleep:
o Changes over lifetime (becomes shorter)
o Function: Depriving first half (more non-REM) – impairs verbal learning
o Depriving second half (more REM) – impairs motor learning
o Function unclear (Possible that function is to move eyes to shake liquid and permit
oxygen to reach cornea)
Lecture 11: Emotion

3 components of emotional processing:

- Cognitions (what you think of situation)
- Action (what you do about situation)
- Feelings
o Distinguish emotions from other mental states (consciousness)
o “Emotion”: subjective internal state; “motivated behaviours” are quantifiable
readouts that serve as proxy for intangible emotion
 Eg. Internal state: positive emotion; External state: more motivated to seek
rewards
 Eg. Internal state: negative emotion; External state: more motivated to avoid
punishment

James-Lange theory of emotion

 What you experience as an emotion is the label you give to your responses
 Event  appraisal (cognitive aspect)  action (behavioural aspect including physiology) 
emotional feeling (feeling aspect)
o Eg. Presented with frightening situation  become aware of automatic responses in
body (eg. heart rate increasing, sweating)  fear
 Subjects with bilateral damage to amygdala  inability to feel fear (no issue with appraisal
or taking action)
 Evidence supporting theory – physiological arousal necessary for emotion?
o People with condition pure autonomic failure – autonomic system fails, claim they
feel emotions but much less intensely (hence decreased autonomic functioning =
decreased emotional feelings)
o People with brain damage preventing voluntary facial movement have trouble
recognising other people’s emotional expressions
 Is physiological arousal sufficient for emotions? – Effect of behaviours on emotions
o People forced to smile thinks jokes are funnier than if they’re not smiling
o Frowning  people rate photographs as more unpleasant
 Supported by experimental evidence; disruptions of autonomic signals and face control
disrupts emotions, and facial expressions also affect emotional assessments

Two-Factor theory of emotion

 Recognition of a salient or arousing stimulus is a distinct process that occurs before valence
processing
o Stimulus  evaluate if it’s important  won’t evoke emotional response if not
salient
o Salient  evaluate valence (good or bad)  decide to avoid or approach
 Misattribution of arousal: male subjects considered female experimenters more attractive
when on a dangerous high bridge
o Hence high arousal occurs at extreme emotions (negative or positive)
 Assign labels of emotions to core effect by contextualising emotions
o Certain kind of states resemble the way they feel internally though we assign different
labels to them
o Eg. Kicked out of university / breaking up; state of arousal…
Brain system supporting emotional processing
 Limbic system: group of brain structures (network of forebrain areas surrounding thalamus)
supporting emotional processing
o Eg. Hippocampus, parahippocampal gyrus, amygdala, frontal lobe, cingulate gyrus,
olfactory bulb etc.
o Involved in autonomic processes, emotional processing, motivation, learning and
memory
 Brain areas are activated by different emotions
o No evidence limbic system functions as integrated system in the mediation of
emotion; efforts to define limbic system failed
 Insula function
o Insula: primary taste cortex – most studies involving disgust emotion find activation
here
o Hence only disgust is localised
 Roles of left and right hemispheres
o Left: behavioural activation system
 Stronger: Happier, more outgoing, more fun-loving
 Damage  trouble identifying other’s emotional expressions
 Marked by low to moderate autonomic arousal
 Marked by tendency to approach
 Eg. happiness / anger
o Right hemisphere: behavioural inhibition system
 Stronger: socially withdrawn, less satisfied with life, prone to unpleasant
emotions
 Damage  better assessment of other’s emotions
 Marked by high autonomic arousal
 Inhibits action
 Eg. fear / disgust

Functions of emotions
- As if emotions were a way our bodies can react to stimuli without having to think about it
- Hence may have evolved to allow us to respond to stimuli important for survivals in ways that
do not require “thinking” about it
o Fear: alerts us to escape from danger
o Anger: directs us to attack intruder
o Disgust: avoid something that might cause illness

Moral decisions:
 Emotions play a large role in feelings we get for moral decisions, as do rational thoughts
 Trolley dilemma: pulling level in trolley to kill one person instead of 5 feels right to most
people, while killing visitor in hospital to save 5 feels wrong to most people  non-rational
feeling governed by emotions
o In switching decisions – using heuristics / emotional response to determine action
 Cultural effects of moral decision making: car crash options
 Culture and environment growing up deeply affects moral decision making, presumably
driven by changes in which the situations and environment affect emotional processing
Damage to prefrontal cortex and emotions
- Man with such damage expressed almost no emotions; frequently made bad decisions that
really cost him (evolutionary advantages of emotion lost)
- Interpersonal relationships (empathising) are important aspects of life that can be affected
with a lack of emotional processing

Attack behaviours
 Build up of activity in the amygdala predisposes to aggressive behaviour
o Amygdala (anterior to hippocampus) identified as a site important for certain aspects
of aggressive behaviours
o Initial threat builds up activity in amygdala  subsequent threats met with faster
aggressive behaviours
 Multiple nuclei in each nucleus serve different functions
o Nature vs nurture environmental influences
o Eg. in violence, heredity and environment interact
 Neurotransmitter (dopamine, norepinephrine and serotonin) levels important to control certain
emotional behaviours eg. aggressiveness; specific enzyme monoamine oxidase A breaks them
down, lowering their available amounts
o Different types have different activity levels  some more efficient than others at
breaking down different neurotransmitters
o People with low levels of MAO A: relationship between early childhood
maltreatment and likelihood of developing antisocial (aggressive and criminal)
behaviours during adulthood, compared to someone with a gene leading to high MAO
A activity
 Aggressive behaviours are a function of an interaction between our genetic makeup and the
environment in which we are raised
 Triple imbalance hypothesis: aggressive behaviour depends on balance of 3 chemicals
(testosterone, cortisol and serotonin)
o Cortisol: stress hormone; decreases is associated with loss of inhibitions (and hence
high aggression)
 High level: perhaps inhibit many behaviours you would otherwise do when
cortisol very low – inhibited whenever you feel like doing
o Those imprisoned for felonies: very aggressive crimes – high testosterone
 o Decreases in serotonin associated with high aggression

Pathway generating serotonin:

 Neurons build serotonin from tryptophan (amino acid that bodies cannot synthesise, only
acquire through diet)
 Tryptophan converted to serotonin
o Chemical by-product generated – molecule 5 hydroxyindoleacetic acid (5-HIAA) that
will be released into blood which is excreted through urine
o Concentration of 5-HIAA in blood relates to how much serotonin is being used (rate
of turnover)
 Serotonin then stored in vesicles, ready to be released at synapses
 Serotonin binds to receptors to generate desired effects, leftovers are reabsorbed
o Hence we produce less serotonin than we use – recycled so no need to produce fresh
o Drugs that block serotonin reabsorption (eg. cocaine) have very strong effects on
cognition
 Serotonin that doesn’t bind or are reabsorbed diffuse in extracellular space; needs to be
replenished (hence convert more tryptophan to serotonin)
o Hence 5-HIAA byproduct which can be measured in blood is associated as measure
of rate of turnover (how much serotonin used in system  the more used, the more
leaks – measure of how much you’re using)
 Serotonin is not a “aggression neurotransmitter”
o Serotonin levels decrease  some depressed, others more aggressive / impulsive /
crave more for drugs
o Hypothesis: serotonin inhibits variety of impulses, low levels remove inhibitions;
resulting behaviour depends on what has been inhibited, which varies from one
person to another

Fear
 Startle reflex: loud noises innately scary
o Stronger if startling sound preceded by another stressful situation (eg. pain),
otherwise might have lower response
o Damage to amygdala abolishes this effect – startle reflex maintained, but no longer
affected by recent experiences
 Amygdala receives input from pain fires, visual and auditory signals  sends projections /
output to:
o Hypothalamus: control of autonomic fear responses (eg. increase in heart rate)
o Prefrontal cortex: approach and avoidance responses
o Midbrain: in turn projects to pons – controls startle reflex, there’s central node that
connects cortical and sub cortical structures to regulate some fear responses
o Hence amygdala plays a role in fear processing, through its deep interconnectivity
with other limbic areas
 Conditions that affect the amygdala
o Toxoplasma gondii: infection that damages amygdala
 Is a protozoan that selectively destroys the amygdala  reduced fear
response  rats trapped by cats more easily
 Evolutionary method: useful for organism’s life cycle – requires infected rats
to be eaten by cats (digestive system allows it to reproduce)
  Someone with damaged amygdala able to feel curiosity and excitement –
governed by other areas in the brain but cannot feel fear
o Kluver-Bucy syndrome: characterised by tame and placid behaviour; development
depends on age, social situation and exact locations of damage
 Damage to amygdala leads to decreased fear response in rats and humans
 Amygdala responds to emotional stimuli (eg. fearful / angry faces)

Anxiety
 A feeling of worry, nervousness, or unease about something with an uncertain outcome
 Most psychological disorders include increased anxiety as a symptom, only anxiety disorders
have it as the only major symptom (eg. GAD, phobia, panic disorder)
 Hypothalamus and limbic system activity related to anxiety
o Seems to be a circuit in hypothalamus where dysfunction leads to anxiety disorders
o Nuclei that generate hormones and control different aspects of autonomic nervous
system
 Relief
o Anxiolytic drugs (anti-anxiety)
 Benzodiazepines eg. diazepam (Valium), chlordiazepoxide (Librium) and
alphazolam (Xanax)
 Bind to GABA receptor, increasing sensitivity to (more affinity for) /
neural transmission of GABA  decreases level of activity of cells
expressing GABA receptors
 Ionotropic channel that allows entry of chloride into cell 
hyperpolarises and inhibits cell  deactivates / prevents activity –
depressing inhibitory neurotransmitter
 Benzodiazepines exert anti-anxiety effects through action in limbic
system
 GABA exerts effect throughout brain, including cortex and thalamus
 Results in side-effects eg. inducing sleepiness, impairing memory
o Anxiety increased by neurotransmitters orexin and CCK (cholecystokinin) in
amygdala / hippocampus, no drugs approved based on them
o Non-pharmaceutical reliefs: exposure therapy (behavioural methods)
Lecture 12: Psychological Disorders

- Biology: genetic propensities

- Environment: family / conditions of upbringing / traumatic events
- Both necessarily have to exert effects through brain systems  have relationship to
behavioural deficits observed

Definition of mental disorder

 From DSM-5: syndrome characterised by clinically significant disturbances in individuals’
cognition, emotion regulation or behaviour
o Syndrome: group of symptoms that consistently co-occur
o Clinically significant: symptoms have to create some serious problems in life (people
have to be unhappy about stuff happening)
 That reflects a dysfunction in the psychological, biological or developmental processes
underlying mental functioning
o Biological: genes, neuroscience
o Developmental: in utero and out of utero processes
 Until about 20s, brain stops generating new connections, starts degenerating
 Mental disorders usually associated with significant distress in social, occupational, or other
important activities (expanding on clinical significance)
 Exceptions:
o An expectable / culturally approved response to a common stressor or loss (eg. death
of loved one) is not a mental disorder
o Socially deviant behaviour (eg. political, religious or sexual) and conflicts that are
primarily between individual and society are not mental disorders unless deviance or
conflict results from a dysfunction in individual as described above
 Eg. find mutation in gene / brain damage / traumatic experience
 Hard to define since we don’t understand underlying causes (only judge
condition based on symptoms, don’t know root cause)

Addictive disorders
 Addiction: strong and harmful need to regularly have or do something
 Substance: alcohol, drugs…
o Exert effects by binding to receptors (Drug affinity: tendency to bind to receptors)
o Agonists: drugs that occupy receptors and activate them (Drug efficacy: tendency to
activate receptors)
o Antagonists: Drugs that occupy receptors but do not activate them; block receptor
activation by agonists
 Brain still producing neurotransmitters, but they cannot bind
 Drug with high affinity and zero efficacy: antagonist – binds to receptor (high
affinity), doesn’t activate it (zero efficacy)
o Agonists + antagonists: some of each effect – overall activation lower
o Drug effects variability: different people have different types of receptors  respond
differently to drugs
 Activities: gaming, gambling, eating, working…
 Common: Compulsive engagement in rewarding stimuli despite adverse consequences
 Affect either dopamine or norepinephrine neurotransmitters
 Drugs affecting synaptic activity:
o Some affect production of neurotransmitters itself
 Eg. Drug AMPT blocks conversion of dopamine
 Eg. Drug DOPA (precursor of dopamine) – increases supply of dopamine
o Some drugs interfere with release of dopamine – when generating dopamine, need to
pack into vesicles which need to fuse
 Eg. Some antidepressants block this reaction converting dopamine into
inactive form  increase concentration of dopamine in cell
 Eg. Drug Reserpine can cause leakage from vesicles, so each has less amount
of dopamine
o Some drugs affect how long dopamine is present in synaptic cleft eg. cocaine,
methylphenidate, tricyclic antidepressants)
 Antidepressants don’t block as many dopamine receptors as cocaine (very
quickly over short period of time)
o Some drugs interfere with receptors itself eg. to prevent neural transmission from
having such a strong effect / provide agonist that will activate receptors even in
absence of neurotransmitters
 Eg. anti-psychotic drugs: block certain receptors eg. dopamine
 Brain structure involved in addiction:
o Nucleus accumbens
 Receives projections from ventral tegmental area (midbrain dopaminergic
region)
 Cells that produce dopamine project to nucleus accumbens, also project to
medial prefrontal cortex
 Sends inhibition back to ventral tegmental area, prefrontal cortex also does so
 Nearly all drug abuse increase activity of dopamine and norepinephrine
synapses
 Opiates (different type of neurotransmitter): don’t directly affect
dopamine and norepinephrine, but end up affecting system
 Nicotine: don’t directly affect dopamine and norepinephrine, affect
systems
 Norepinephrine also released here
 Activity here increases when drugs consumed
 Also responds to many other types of pleasant experiences (sexual
excitement, music, taste of sugar), drugs hijack normal pleasure centre
o Basal ganglia (part of the ventral striatum)
o Amygdala
 Receives glutaminergic input from VTA, sends it to nucleus accumbens –
core region in between dopaminergic ascending modulatory system and
prefrontal regions
 Repeated exposure to addictive substances may
o Increase number of receptors GABAergic neurons in nucleus accumbens
o Increase receptor sensitivity
o Increase metabolism of substance in bloodstream (eg. alcohol)
 Developing drug tolerance (as opposed to oversensitivity): body now used to receiving certain
amount of drug as molecular structure biochemical pathways modified – when needing to
 stop may experience withdrawal symptoms (shaking, vomiting, fatigue, hallucinations,
convulsions)
o Increase number of receptors that capture neurotransmitter / drug: downstream effects
of changes (how cell responds to activation of receptors) may change – now require
more
 Analysing risk factors
o Eg. offspring’s propensity of alcoholism – measure genetic / physiological
differences between reactions to alcohol to see how different manipulations / life
events may affect likelihood of addiction (genes)
o Environment including that during prenatal, childhood and adulthood critical too

Depressive disorders
 Group of disorders characterised by presence of sad, empty or irritable mood which
significantly affects individual’s function
 For long periods of time very often
 Does not enjoy anything / cannot imagine enjoying anything
 Fatigue, feelings of worthlessness, contemplation of suicide
 Trouble sleeping / concentrating
 Some suffer long term, though more common to have periodic episodes
 Risk factors:
o Genetic: many depression-related genes identified, but each very small effect
 Early-onset depression (before 30): likely to have relatives with depression –
stronger genetic factor
 Late-onset depression (after 45): linked to relatives with circulatory problems
(regulation in certain parts of the brain eg. low blood supply)
o Environmental: stressful events can precipitate depression in vulnerable individuals
 Young adults with short form of serotonin transporter gene (variant) who
experienced stressful experiences had major increase in probability of
developing depression
 Heterozygous: somewhere in between
 Antidepressants:
o Don’t directly improve mood – increase levels of neurotransmitters very fast, but
improvements in mood may take much longer (eg. weeks)
o Most common alter serotonin and/or norepinephrine neurotransmission
o Eg. Serotonin/norepinephrine reuptake inhibitors – allow them to be in synaptic cleft
longer: duloxetine (Cymbalta) and venlafaxine (Effexor)
o Drugs selective to serotonin (inhibition) only  less side effects: fluoxetine (Prozac),
sertraline (Zoloft), fluvoxamine (luvax), citalopram (celexa), paroxetine (paxil)
o Are they effective?
 Mild severity: tend to become worse / not improve
 Middle range: not much difference
 Severe depression: clear effects
 Alternatives to antidepressants:
o Cognitive-Behavioural Therapy (CBT): strong antidepressant benefits (on par with
drugs, so combined)
 Preferred over drugs – no side effects, lower likelihood of relapse after
therapy over
 o Exercise: modest antidepressant benefits
o Electroconvulsive therapy: applying electric shocks in brain (last resort – shuffling
the brain, sometimes leads to improvements)
o Non-invasive method: Transcranial magnetic stimulation (TMS) – activating certain
parts of brain, only superficial parts though (parts unable to reach: middle prefrontal
cortex, anterior cingulate cortex, ventral striatum,…)
o Deep brain stimulation – put electrode in brain region you think is relevant for
depression, put pacemaker at chest and regularly emits pulse of electricity
o Vagus nerve stimulation (parasympathetic main nerve that goes through neck)
o If drugs and behavioural treatment do not work, seek experimental treatment eg. deep
brain stimulation

Schizophrenia
 Deteriorating ability to function in everyday life for at least six months, paired with at least
two of following symptoms, including at least one of first 3:
o Hallucinations (eg. hearing voices)
o Delusions (unjustifiable beliefs)
o Disorganised speech
o Grossly disorganised behaviour
o Weak / absent signs of emotion, speech and socialisation
o First 4: positive symptoms – behaviours present that should be absent
 Hypothesis: Disorganised thought is core of schizophrenia, due to dysfunction of working
memory (due to abnormal connections between cortex, thalamus and cerebellum)
o Could be due to mutations in certain genes / neurotransmitters / receptors
 Unexplained epidemiological observations:
o Significantly less common than average in people with type 1 (juvenile-onset)
diabetes, but more common in people with type 2
o Increased risk of colon cancer, but below average probability of respiratory / brain
cancer
o Seldom develop rheumatoid arthritis / allergies
o Those with breakdowns during pregnancy usually give birth to daughters, if shortly
after usually sons
o Have characteristic body odour (dogs can smell) – chemical specific
o Most and their unaffected relatives in pursuit eye movements (ability to keep eyes on
moving target)
 Risk factors
o More closely related biologically to someone with it, greater own probability of
having it
o Environment also plays important role (perhaps not as much as genetics)
o New mutations most likely mechanism (rather than inheriting mutated genes from
parents) – family risk less effect than upbringing
 Neurodevelopmental hypothesis: important factor in development of schizophrenia is
disturbance in development (in-utero / early childhood)
o Poor nutrition / substance abuse / stress / infections / fevers during pregnancy
o Owning cats during childhood (could be toxoplasma gondii)
 Dopamine hypothesis: drugs that block dopamine synapses work as antipsychotic (higher
affinity of drugs, lower concentration needed)
 o Increased dopamine release during first psychotic episodes
o Abusing drugs cause symptoms very similar to schizophrenia – eg. overdosing on
cocaine(affects dopamine in brain – experience brief episodes like psychotic ones)
 Glutamate hypothesis: deficient activity of glutamate synapses in prefrontal cortex are causes
o Drugs blocking dopamine also affect glutamate neural transmission (NMDA
inhibitors)
o Disorder associated with less release of glutamate and less NMDA receptors

Autism Spectrum disorder

 Deficits in social and emotional exchange
 Deficits in gestures, facial expressions and other non-verbal communication
 Stereotyped behaviours eg. repetitive movements
 Resistance to change in routine
 Unusually weak / strong responses to stimuli eg. indifference to pain / panicked reaction to
sound
 Risk factors
o Genetic: genes identified, but small effect
 Appears that new mutations (rather than those inherited) responsible for
autism, like in schizophrenia
o Environmental: Prenatal very important (eg. antibodies attacking certain brain
proteins)
 Folic acid (vitamin B9) reduces risk of autism by half