Behavioral Neuroscience

PSB 3340 - Fall 2019

Week 1
The Neuron
& Action potential

Marek Schwendt, PhD

Lecture outline

▪ Neurons and Glia - Specialized Cells That Make

Up the Nervous System
▪ Membrane potential
▪ Action Potential
▪ Electrical Signals Within the Network of
Neurons – normal and abnormal (disease)
What are the cells in the brain? 19th-century ideas & discovery

Camillo Golgi
(1843-1926, Italian biologist & pathologist)

Ramón y Cajal
(1852-1934, Spanish neuroanatomist)

“Neuron doctrine” states that:

The brain is composed of
independent cells &
that information is transmitted
from cell to cell across synapses.
Specialized Cells Make Up the Nervous System

Neurons, or nerve cells, are the most important part of the

nervous system. (~86 Billion neurons in Hu brain)
Glial cells provide support for and contribute to
information processing neurons (1:1 ratio of glia and
neurons).

link
Specialized Cells Make Up the Nervous System

Neuron – just another cell…

A neuron has structures in common with other cells:
• Mitochondria—produce energy
• Cell nucleus—contains genetic instructions
• Ribosomes—translate genetic instructions into
proteins
The Principal Components of Neurons

Neuron –
highly
specialized &
unique cell…
Neurons and their function

Neurons vary in function.

• Motor neurons stimulate muscles or glands.

• Sensory neurons respond to environmental

stimuli, such as light, odor, or touch.

• Interneurons receive input from and send input to

other neurons.
Technical Note: Visualizing the Cells of the Brain

Note: Visualizing the Cells of the Brain

Advancements in histology have enabled selective
staining of parts of neurons and glia.
Counting cells in brain regions:

Nissl stains outline ALL cell

bodies because the dyes are
attracted to RNA, which
encircles the nucleus.
Technical Note: Visualizing the Cells of the Brain

Examining forms of individual cells in the brain:

• Golgi stains fill the whole cell, revealing details,
(only a small proportion of neurons stained).
Technical Note: Visualizing the Cells of the Brain

Examining forms (and identity) of individual cells in the brain.

Immunohistochemistry (IHC) detects a protein in tissue.

Rat hippocampus
stained with
antibody against
NeuN (green),
myelin basic
protein (red) and
DNA (blue).
Technical Note: Visualizing the Cells of the Brain

Examining forms (and identity) of individual cells in the brain.

Transgenic animals expressing fluorescent protein
Technical Note: Visualizing the Cells of the Brain

Tracing interconnections between neurons:

Tract tracers are substances taken up by neurons and
transported through their axons.
• Anterograde labeling reveals the axonal targets of cell
bodies in a particular region.
• Retrograde labeling reveals the cell bodies of axons
terminating in a region.

Some tract tracers

can work trans-synaptically.
Technical Note: Visualizing the Cells of the Brain
Figure 2.5 Synapses (Part 1)
Figure 2.5 Synapses (Part 2)

Components of the synapse:

Figure 2.6 Axonal Transport

Axon hillock: A cone-

shaped area of the cell
body that gives rise to
the axon.
The one axon often
divides into axon
collaterals, allowing
the neuron to
innervate more than
one postsynaptic cell.
Axonal transport: The
movement of materials
within an axon via
motor proteins.
Table 2.1 Distinctions between Axons and Dendrites
Types of Glial cells. Part 1

▪ “The four main functions of glial cells are: to

surround neurons and hold them in place, to supply
nutrients and oxygen to neurons, to insulate one
neuron from another, and to destroy and remove the
carcasses of dead neurons (clean up).”

▪ NEW: can communicate with each other and with neurons (link).
Types of Glial cells. Part 1

4 kinds of glial cells:

• Astrocytes, or
astroglia: Star-shaped
cells with many
processes that receive
neuronal input and
monitor activity.
• Microglial cells, or
microglia: Small cells
that remove debris from
injured cells.
Types of Glial cells. Part 2

▪ Oligodendrocytes are glial

cells that form myelin sheath
in the brain and spinal cord.

Myelination: The process in which glial cells wrap axons with a fatty
sheath, myelin, to insulate and speed conduction.
Nodes of Ranvier: Gaps between sections of myelin -the axon is exposed.
Types of Glial cells. Part 3

▪ Schwann cells provide

myelin to cells outside the
brain and spinal cord.
Glial cells & brain pathologies

▪ respond to injury by edema, or swelling

▪ are also susceptible to tumors.
▪ Astrocytes influence brain chemistry and have been
implicated in epilepsy.
▪ Microglia have been implicated in degenerative disease,
such as Alzheimer’s.
▪ Multiple sclerosis: A demyelinating disease.

OK, that is all good…but why do we care about

glia in behavioral neuroscience? (few examples)
motor learning addiction
Resting membrane potential
and
action potential
Experiment - Measuring neuronal membrane potential

“resting membrane potential”

Cell membrane:
phospholipid bilayer
&
selective barrier
transport
mechanisms
exist…

…still it is a
selectively
permeable
membrane (some
ions cross more
freely than others)
Notes on the membrane potential

Two opposing forces drive

ion movement:

• Diffusion causes ions to

flow from areas of high to
low concentration, along
their concentration
gradient.

• Electrostatic pressure
causes ions to flow
towards oppositely
charged areas.
Notes on the membrane potential

• While membrane potential is present in all cells, it is

especially important in nerve and muscles cells,
because … changes in their membrane potentials are
used to code and transmit information.

• only a very small number of negative and positive ions

need to be separated by the membrane to create the
resting membrane potential.

• E.g. for each pair of negative and positive ions

separated by the membrane, there are roughly 1000
pairs of positive and negative ions within the cytosol of
the neuron.
Resting Membrane Potential in Neurons

Neurons:
Some channels are open all the time and allow only
potassium ions (K+) to cross.
The neuron shows selective permeability—it allows
K+ to enter or leave the cell freely but restricts the
flow of other ions.
Figure 3.3 The ionic basis of the resting potential (Part 1)

Neurons use a
mechanism called
the sodium-
potassium pump
to maintain
resting potential.
It pumps three
sodium ions
(Na+) out for
every two K+ ions
pumped in.
Figure 3.3 The ionic basis of the resting potential (Part 2)

At rest, K+ ions move into

the negative interior of the
cell because of
electrostatic pressure.
As K+ ions build up inside
the cell, they also diffuse
out through the
membrane, along the
concentration gradient.
Figure 3.3 The ionic basis of the resting potential (Part 3)

K+ reaches
equilibrium when
the movement out
is balanced by the
movement in.
This corresponds to
the resting
membrane
potential of about
–60 mV (values
range between –50
and –80 mV).
The Resting Membrane Potential - Nernst Equation

The Nernst equation predicts the voltage needed to

counterbalance the diffusion force pushing an ion
across a membrane.
• Predicts the equilibrium potential of an ion,
usually K+.
The equation predicts a potential of –80 mV.
The measured equilibrium potential of neurons is
typically closer to –65 mV.

More on this click here

The Resting Membrane Potential – Goldman Equation

The Goldman equation predicts voltage potentials

that are quite close to observed resting potentials.
• The Goldman equation takes into account the
intracellular and extracellular concentrations of
several ions and the degree of membrane
permeability to each.

• Example:
Figure 3.4 The distribution of ions inside and outside of a neuron
Action potential
Action Potentials

Action potentials:
• brief but large changes in membrane potential.
• originate in the axon hillock and are propagated
along the axon.
• patterns of action potentials carry information to
postsynaptic targets.

“Electrical Signals Are the Vocabulary of the Nervous

System”
Action Potentials – changes in membrane potentials

Hyperpolarization is an increase in membrane

potential—the interior of the membrane becomes
even more negative, relative to the outside.
Depolarization is a decrease in membrane
potential—the interior of the cell becomes less
negative.
Action Potentials – Local potential

Local potential: An electrical potential that

spreads passively across the membrane,
diminishing as it moves away from the point
of stimulation.
Action Potentials – The Threshold

Depolarizing stimuli produce local, graded responses.

If the membrane potential reaches the threshold
(about –40 mV), an action potential is triggered.
The membrane potential reverses and the inside of
the cell becomes positive.
Action Potentials – All-or-none

All-or-none property of action potential

• Neuron fires at full amplitude or not at all.
• Does not reflect increased stimulus strength.

Information is coded in the frequency of action potentials.

• Increased frequency = increased stimulus strength

‘Afterpotentials’ are changes in membrane potential

after action potentials.
Action Potentials - Phases

Action potentials are produced by the movement of Na+

ions into the cell.
At the peak of an action potential, the concentration
gradient pushing Na+ ions into the cell equals the
positive charge driving them out.
Membrane shifts briefly from a resting state to an active
state and back.
Action Potentials - Voltage-gated Na+ channels

Voltage-gated Na+ channels open in response to the

initial depolarization.
More voltage-gated channels open and more Na+ ions
enter.
This continues until the membrane potential reaches the
Na+ equilibrium potential of +40 mV.
Action Potentials – Going back to Resting Potential

As the inside of the cell becomes more positive,

voltage-gated K+ channels open.
K+ moves out and the resting potential is restored.
Figure 3.6 Mediation of the action potential by voltage-gated sodium channels
Action Potentials - Phases
Action Potentials – Refractory Period

Refractory period: Time when only some

stimuli can produce an action potential.
Absolute refractory phase: Time when no
action potentials are produced.
Relative refractory phase: Time when only
strong stimulation can produce an action
potential.
Action Potentials – Propagation
Action potentials are regenerated along the axon -
each adjacent section is depolarized and a new
action potential occurs.
Action potentials travel in one direction because of the
refractory state of the membrane after a
depolarization.
Figure 3.8 Conduction along unmyelinated axons and saltatory
conduction along myelinated axons (Part 1)
Figure 3.8 Conduction along unmyelinated axons and saltatory
conduction along myelinated axons (Part 2)
Action Potentials - Propagation

Conduction velocity: The speed of

propagation of action potentials - varies with
diameter.
Nodes of Ranvier: Small gaps in the
insulating myelin sheath.
Saltatory (latin: leap or jump) conduction: The
axon potential travels inside the axon and
jumps from node to node.
Some Chemicals (drugs, toxins) Can Block Action Potentials

Animal toxins selectively block certain channels:

• Tetrodotoxin (TTX) and saxitoxin (STX) block
voltage-gated Na+ channels.
• Batrachotoxin forces Na+ channels to stay open.

• Cocaine, lidocaine

Lidocaine

Cocaine 1
Cocaine 2
Figure 3.10 Integration of excitatory and inhibitory inputs

.
Synapse
EPSPs
IPSPs
Spatial summation
Neurotransmitters
Neurons and Synapses Combine to Make Circuits

Clarity technique 1 Diffusion Tensor Imaging (DTI) –

can be used for Fiber Tracking
MRI-based neuroimaging technique -estimates
Clarity technique 2 the location, orientation, and anisotropy of the
brain's white matter tracts. Diffusion of the water
molecules along axons…
Technical note: EEG

An encephalogram (EEG) is a recording of brain

potentials, or brain waves (~ Gross Electrical Activity
of the Brain)
Brain potentials indicate sleep states and provide data
in seizure disorders.
Technical Note: EEG
Figure 3.20 Gross potentials of the human nervous system
Technical Note: EEG
Figure 3.21 Discharge patterns during seizures (Part 1)
Technical Note: Electrophysiology
Detailed measurement of neuronal activity (e.g. APs)

Whole-cell recording
from a CA1 pyramidal
neuron in the
hippocampus during
exploration of an oval
track. Firing patterns of
‘‘place cells’’.

Lee et al.(2012)
Tech Note: Voltage-sensitive dyes allows for imaging of APs

https://youtu.be/t3TaMU_qXMc

“Voltage-sensitive dyes are dyes

(typically organic molecules or proteins)
which change their spectral (optical)
properties in response to voltage
changes”

Wikipedia