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COLLEGE OF ALLIED MEDICAL PROFESSIONS

University of the Philippines Manila


Bachelor of Science in Physical Therapy Class of 2017






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[02]: Neurophysiology 1 Dr. Darwin Dasig 20 Aug 2014 Physio 21
Topics
I. The Nervous system
II. Resting membrane potential
III. Local potential
IV. Action potential or Nerve impulse
V. Synapse and Synaptic transmission
VI. Somatosensory system

I. THE NERVOUS SYSTEM
It is used for:
Control of the body.
Integration
Integrates all the systems in order to
maintain homeostasis
It is Contralateral.
It senses danger from the external
environment and reacts accordingly in the
other direction
The right brain controls the left side of the
body and vice-versa
It interacts with the internal and external
environment in order to maintain homeostasis.
It is composed of the Brain, Brain stem, Spinal
cord, nerves and muscles.
Brain
Serves many different functions.
It is comprised of Neurons.
These are the functional part of the
brain.
It has a Cell Body (Soma).
Contains the nucleus.
Metabolic center of the cell.
Controls all the maintenance of
the neuron.
It has several processes called
Dendrites which extend outward
and becomes a receptive area for
an adjacent axon.
It also has a long process called an
Axon that originates from the Axon
Hillock.
Action potentials / Conducted
impulses generate in the initial
segment of the axon.
This divides into presynaptic
terminals, each of which ends in a
number of synaptic knobs/terminal
buttons or boutons.
Can be classified into unipolar,
bipolar, or multipolar.



Axons can end either on another
neuron or into an effect organ.
Neurons function via:
Electrical signals
Local potential
Nerve impulse/Action Potential
Chemical signals
Synaptic transmission
Works in an All/None Response

II. RESTING MEMBRANE POTENTIAL
In order generate a potential difference across
the membrane of the cell, there are two
conditions that must be met.
There is an unequal distribution of ions of
one or more species across the membrane
(Concentration gradient).
The membrane must be permeable to one
or more ions.
Permeability is provided by the
presence of channels that may be open
or closed via voltage gauge.






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[02]: Neurophysiology 1 Physio 21 UPM PT 2017
The resting membrane potential of any neuron
is usually -70mV.
Plasma membrane
Composed of Phospholipids.
Phospholipids have polar head
(Hydrophilic) and 2 non-polar tails
comprised of fatty acyl chains
(Hydrophobic).
They are amphiphatic.
Can combine to form a circular shape
with the hydrophilic head on the
outside or into a more stable lipid
bilayer with the heads on the outside.
This formation would not allow
charged/polar molecules to cross
the lipid bilayer.
Structural proteins are present in
order to allow charged or large
particles to pass through.
Small and non-charged particles
are the only ones able to pass
through this bilayer.
The permeability of the membrane for ion
species (K
+
,Na
+
,Cl
-
) contribute to the charge
of the resting membrane potential.
K
+
ions are intracellular.
Na
+
, Cl
-
ions are extracellular.
No Na
+
leak channels are present
(Voltage gauged only).
K
+
and Cl
-
can move freely through the
plasma membrane.

Gibbs-Donnan Equilibrium
In the presence of a non-diffusible ion,
diffusible ions distribute themselves so that
at equilibrium, their concentrations are
equal.
This is affected by the concentration and
electrical gradient.
K
+
and Cl
-
ions can move freely through the
membrane. But negatively charged
proteins that are present in the membrane
prevent Cl
-
ions from moving inward,
resulting in their extracellular nature.
[K
+
]
i =
[Cl
-
]
o

[K
+
]
o
[Cl
-
]
i

Donnan Effect
Refers to the asymmetric distribution of
permeant ions at equilibrium.
Electrical difference across the membrane
with magnitude is determined by Nernst
equation.
Transmembrane Potassium Ion Gradient thru
Non-Gated Potassium Ion Leak Channels
Nernst equation
Diffusion Pressure
W
d
= RT (l
n
[C]
hi
l
n
[C]
lo
)
Electric Pressure
W
e
= (E
m
) (Z
i
) (F) E
m
=
absolute membrane potential; Z
i
=
valence (number of charges on the
ion); F = faraday (number of
coulombs per mol of ion)
At equilibrium:
There is no net movement.
Diffusion pressure = Electrical
pressure.
This is used to determine the
equilibrium potential of a single
diffusible ion (The potential dictates
the direction of the motion that the
ions follow to attain equilibrium).
K
+
= - 90 mV
Moves outside via leak
channels.
Na
+
= + 60 mV
Moves inward via gated
channels.
Cl
-
= - 70 mV
No net movement.
In equilibrium with the RMP
* Leak channels allow free movement of the ion
* The Membrane potential at rest depends
primarily on the transmembrane potassium ion






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[02]: Neurophysiology 1 Physio 21 UPM PT 2017
gradient thru non-gated potassium ion leak
channels
K+ leak channels
Open and closed voltage-gauged channels
K+ ions can move freely but the RMP doesnt
reach the equilibrium potential of K+ because
Na+ can move and leak In the membrane in
small quantities
Na+ ions has no leak channels only voltage-
gauged channels are present
Resting membrane potential via Goldman Constant
field equation
This equation takes into account all the
permeabilities of the ions present in and out of
the cell.
Takes into account the concentration ratios of
each of the ions.





*K
+
moves out freely allow the RMP to move to -90mV while
Na
+
ions move inward in small quantities to revert the RMP
back to -70mV.


Na
+
-K
+
ATPase pump
Converts ATP to ADP and P to actively transport 3
Na+ ions out and 2 K+ ions in which results in a net
loss of +1 charge inside the cell.
This maintains the difference in concentration of
Na+ and K+ and the negativity of the inside of the
cell.
Most important part of the RMP.
The asymmetry of the concentrations results in
the electric charge.



The resting membrane potential is not in equilibrium.
The RMP is only a steady state due to the presence
of the ATPase pump.
Due to the usage of ATP (Equilibrium doesnt need
energy in order to be maintained).

III. LOCAL POTENTIAL
Local Potential
Transient shift of the membrane potential
in a localized area of the cell (quick
change).
Change in one portion of the membrane
(any kind of change).
Lygan change a neurotransmitter
combines with receptor that opens
(synaptic potential).
Graded response amplitude is
proportional to size of stimulus (more to
more).






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[02]: Neurophysiology 1 Physio 21 UPM PT 2017
Hyperpolarization depolarization
(hyper = increase negativity)
Rapid long


Local Potential Kickoff
Local change in permeability of the membrane to 1
or more ions.
Synaptic potential
Lygan change
Generator potential
chemical change
Change in voltage/current applied from a source.
Electrotonic potential
Add voltage
*increase Na and K conductance =
depolarization due to high driving force of
Na (lesser degree when increased Na
conductance).
Local Potentials
Change in potential develops and subsides over a
few milliseconds.
Remain localized in region where stimulus is
applied.
Not sharply confined: falls off over a finite distance
on the membrane.
Within milliseconds and within a single area.
Voltage change = current X resistance
Some ions leak out across membrane.
Lesser charges reach more distant
sites.
stable resistance : decreased current
decreased voltage
Local potential (Voltage change) decreases
with distance from the point of stimulation
Space constant
Describes the distance of the voltage change along
the membrane.
Distance at which the initial transmembrane
voltage change has fallen to 37% of its peak value.
The larger the space constant, the farther along
the membrane a voltage change is observed after
a stimulus is applied.
Limit of the local potential (distance away the
body).



R
m
= transmembrane resistance (ohm-cm)
R
a
= internal axoplasmic resistance (ohm/cm)

Diameter of axon or dendrite
R
a
(internal axoplasmic resistance)
space constant
current will flow farther along cell
R
m
(transmembrane resistance)
space constant
less current leaks out
Directly related to the transmembrane resistance.
High transmembrane resistance longer
distance (how easy to leave; barrier will
squish them out).
Low Internal axoplasmic resistance high
distance (how easy to travel; inside is very
spacious).

Local Potentials CAN BE SUMMATED!
Spatial summation
Add up beside each other (through space).
Remain localized in region where stimulus is
applied.
Not sharply confined: falls off over a finite
distance on the membrane.
Temporal summation
Change in potential develops and subsides
over a few milliseconds.
Same space (through time)
Repeated stimulation














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[02]: Neurophysiology 1 Physio 21 UPM PT 2017

*Spatial summation (top) and temporal summation
(bottom)
*summated subthreshold potentials may reach
threshold and produce an action potential
*neurons = electrical and chemical communication

IV. Action potential or Nerve impulse
ACTION POTENTIAL
Fleeting, self-renewing wave of membrane
depolarization that propagates without
decrement along the length of a nerve
axon at high speed.
Is a rapid, all-or-none change in the
membrane potential followed by a return
to the resting membrane potential.

Voltage-dependent ion (Na
+
and K
+
)
channels in the plasma membrane are the
basis for action potentials.










An action potential is propagated with the
same shape and size along the entire
length of an axon.
Action potentials are usually initiated at the
axon hillock of the axon.
The action potential is the basis of the
signal- carrying ability of nerve cells.
The patterns of conducted action
potentials encode the information
conveyed by nerve cells.













Spike Potential
Sharp rise and rapid fall of the membrane
potential.






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[02]: Neurophysiology 1 Physio 21 UPM PT 2017


Refractory Period
Absolute
Threshold to one-third of repolarization.
No stimulus will excite the nerve.
Relative
Up to start of after-depolarization.
Stronger than normal stimulus can cause
excitation.

After-depolarization
Slower fall at end of spike potential.
supernormal period
After-hyperpolarization
Overshooting of membrane repolarization after
reaching resting level.
subnormal period
All or None Law
Full-pledged AP produced once threshold intensity
is reached.
Further increase in intensity of stimulus does not
produce increment or other change in AP.
No AP if stimulus is subthreshold in magnitude.
Constant amplitude and form.










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[02]: Neurophysiology 1 Physio 21 UPM PT 2017






Speed of Action Potential Propagation
diameter of axon
* diameter cytoplasmic resistance flow of
ions length of axon depolarized (space constant)
time needed for AP to travel along axon



















myelin
effective resistance of axonal membrane
(transmembrane resistance R
m
): ions must
flow through myelin before reaching ECF
space constant
effective capacitance of axonal
membrane: distance between ICF & ECF
time constant
conduction velocity
unmyelinated axons
Voltage gated Na
+
and K
+
ion channels
distributed uniformly along length of
axonal membrane.
myelinated axons
High concentration of voltage-gated Na
+
and
K
+
ion channels in axon hillock & nodes of
Ranvier.
low density along internode









Saltatory Conduction
Myelinated axons
myelinated: axons > 1m diameter
conduction velocities:myelinated = 3 120
m/sec; unmyelinated = 0.5 2.0 m/sec











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[02]: Neurophysiology 1 Physio 21 UPM PT 2017
V. SYNAPSE AND SYNAPTIC TRANSMISSION
Synapse - A junction where the axon or some other
portion of one neuron (called the presynaptic
neuron) terminates on the dendrites, soma, or axon
of another neuron (called the postsynaptic neuron),
muscle cell, or gland cell.
Types of Synapses
Electrical
There is a gap junction formed between the
presynaptic and postsynaptic neuron.
There is cytoplasmic continuity.
Since the neurons are connected to each
other, they are inflexible (they cannot form
new connections).
Each gap junction is formed by two
hemichannels called Connexons, one
contributed by each cell.
The gap junction forms low-resistance
bridges through which ions pass with relative
ease.
There is very little distance between the
two neurons (3nm-5nm).
Ionic currents travel extremely fast
through these bridges.
There is no synaptic delay.
The structure allows for the bidirectional
travel of the ionic currents.
Uses very little metabolic energy and
molecular machinery.
Highly reliable.

Chemical
Presynaptic and postsynaptic neurons are
separated by a space called the Synaptic Cleft.
There is no cytoplasmic continuity.
Since the neurons are separated from
each other, they are flexible (they can
form new connections as required, such as
when learning new skills or remembering
something). This is termed Plasticity.
The presynaptic neuron uses chemical
transmitters called Neurotransmitters
that bind to the postsynaptic neuron to
propagate potentials.
Neurotransmitters are able to travel much
larger distances (30nm-50nm) between
the presynaptic and postsynaptic neuron.
The neurotransmitter is unidirectional:
from the presynaptic neuron to the
postsynaptic neuron.
They are capable of amplifying or inhibiting
signals.
They can transmit information over a broad
time domain.
They exhibit Plasticity.
Refers to the synaptic strength function of
recent neural activity.
It plays a role in learning and memory.
Essential to the success of the vertebrate
species.



Kinds of Synapses Based on Location
Inhibitory synapses nearer to the axon hillock
Axo-somatic (axon to the soma) most
inhibitory
Excitatory synapses near the dendrites
Axo-dendritic (axon to a dendrite) most
excitatory
Axo-axonal (axon to another axon)
Dendro-dendritic (a dendrite to another dendrite;
rare)
Soma-somatic (the soma to another soma; rare)
Dendro-somatic (a dendrite to a soma)







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[02]: Neurophysiology 1 Physio 21 UPM PT 2017


Neurotransmitters
Stored in synaptic vesicles.
Released into the synaptic cleft with the nerve
impulse.
Act on appropriate receptors on the
postsynaptic membrane.
Different Neurotransmitters
Small-molecule transmitters
Monoamines (Acetylcholine, Serotonin,
Histamine)
Catecholamines (Dopamine,
Epinephrine, Norepinephrine)
Amino Acids (Glutamate, GABA, Glycine)
Large-Molecule transmitters
Neuropeptides (Substance P,
Enkephalin, Vasopressin)
Glutamate The main excitatory transmitter.
GABA (Gamma-Aminobutyric Acid) The main
inhibitory transmitter.
Neuromodulators
Chemicals released by neurons with little or no
direct effects on their own, but can modify the
effects of neurotransmitters.
Transmitter Release
Mechanism
The action potential opens voltage-
gated Ca
2+
channels at the end of the
axon.
The axon allows Ca
2+
to enter.
This increases the Ca
2+
intracellular
concentration.
The increased Ca
2+
level triggers the
binding of synaptic vesicles to the
membrane.
The neurotransmitters inside the
synaptic vesicles are then released to
the synaptic cleft via exocytosis.

Various Structures Involved
Synaptotagmin
The synaptic vesicles Ca
2+
sensor.
It binds proteins that cause the
vesicles to dock and bind to the
presynaptic terminal membrane.
SNAREs
These are tethers employed by the
synaptic vesicle and the presynaptic
neurons cell membrane to ensure
that the vesicle reaches the cell
membrane.
Vesicle SNARE (v-SNARE)
Synaptobrevin
Terminal membrane SNARE (t-
SNARE)
Syntaxin
SNAP-25
Snare Mechanism
Initial State
The vesicle moves to the nerve
terminal membrane, which contains
Syntaxin and SNAP-25 (t-SNAREs).
Formation of the Ternary Complex of
Snares
N-sec-1 (a protein in Syntaxin),
dissociates from Syntaxin.
This allows the Syntaxin and
the SNAP-25 to form a complex.
The distal end of the
Synaptobrevin begins to wind
around the Syntaxin-SNAP-25
complex. This results in a
ternary complex.
Tightening of the Ternary Snare Complex
The three SNAREs continue to form
a tight bundle of helices.






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[02]: Neurophysiology 1 Physio 21 UPM PT 2017
The vesicle is further drawn to the
presynaptic membrane.
Fusion and Exocytosis
The entry of Ca
2+
via voltage-gated
channels causes an influx of Calcium
that binds to Synaptotagmin.
This triggers fusion of the vesicle
and the cell membrane, and
consequent exocytosis of the
neurotransmitter.
Disassembly of the Ternary Snare
Complex
-SNAP and the ATPase NSF bind to
the ternary SNARE complex.
They use the energy of ATP
hydrolysis to disassemble the
SNAREs.
Recycling of Snares
The vesicle is endocytosed, and the
three SNAREs are again ready for
use.
Additional Information
Transmitter release is a quantum.
The number of neurotransmitter
molecules released by one vesicle is
fixed.
Even if the neurotransmitters are
quantized (Quantum Content), the
number of quanta released when the
synapse is activated depends on the
level of Ca
2+
.
The greater the Ca
2+
, the more
quantized neurotransmitters are
released.
Burst of transmission terminates with
rapid sequestration in organelles (such
as the mitochondria) within the ending.
Ca
2+
is extruded via the Na
+
- Ca
2+
Antiport.

Neurotransmitter Receptors
Ionotropic Receptors
The chemical receptor is also the
channel.
Ligand-gated ion channel proteins
Rapid opening of ion channels
Depolarization and hyperpolarization
Nicotinic Acetylcholine, GABA, Glycine,
Serotonin, Glutamate
Metabotropic Receptors
The chemical receptor is not the
channel.
The cell membrane uses proteins to
facilitate the channeling of the
neurotransmitter.
Seven-transmembrane-helix-receptors
G protein-linked
G proteins are nucleotide regulatory
proteins that bind GTP.
Ion channel proteins or 2
nd
messenger
effector proteins
Translate signals to biological
effects inside the cell.
Glutamate, Muscarinic Acetylcholine,
and adrenergic
Excitatory Postsynaptic Potential (EPSP)
Local potential of depolarization under the
active zone from a single stimulus.
Increases the excitability of the neuron to other
stimuli.
Ionic basis:
Na
+
channels are opened.
There is an increase in Na
+
conductance
through ligand-gated channels.
Closure of K
+
channels.
Inhibitory Postsynaptic Potentials (IPSP)
Local potential of hyperpolarization
Postsynaptic direct inhibition.
Stimulation to other stimuli is decreased.
Ionic basis:
Opening of CI
-
channels.
There is an increase in Cl
-
conductance
causing an outward flow of current.
Opening of K
+
channels.
Closure of Na
+
or Ca
2+
channels.
Excitation
Spatial and Temporal summation.
Spatial summation refers to excitation
over an area, where intersecting areas
of excitation in the postsynaptic neuron
are added-up.
Temporal summation refers to repeated
excitation over time.
The axon hillock is the area of highest
integration

Inhibition
Presynaptic Inhibition






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[02]: Neurophysiology 1 Physio 21 UPM PT 2017
Provides a mechanism for controlling
the efficacy of transmission at individual
synapses.
Mediated by Axo-axonal synapses.
Postsynaptic Inhibition
Direct Inhibition
Inhibition with IPSP
Not a consequence of previous
discharges of the postsynaptic
neuron.
Indirect Inhibition
Due to the effects of previous
postsynaptic neuron discharge
(refractory period or during after-
hyperpolarization).
Long-term Potentiation
Characterized by the enhanced transmission at
synapses that follow high frequency
stimulations.
First observed in the hippocampus, a
part of the brain that plays an important
role in memory.
Depends on the presence of NMDA (N-methyl-D-
aspartate) receptors in the postsynaptic
membrane.
Plays a role in memory and associative learning.
Convergence and Divergence
One to one.
Divergence:
One to many The axon of the
presynaptic neuron divides into many
branches that end on many
postsynaptic neurons.
Spatially focused The branching is
much less, usually confined to several
effectors in close proximity.
Widely divergent The branching goes
over a wide area.



Convergence:
Many to one Many presynaptic
neurons converge on a single
postsynaptic neuron.




























REFERENCES:

Barret, K.E., Barman, S.M., Biotano, S., & company. (2012).
Ganongs Review of Medical Physiology, 24
th
ed. The McGraw-
Hill Companies, Inc., United States of America.







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[02]: Neurophysiology 1 Physio 21 UPM PT 2017
Dasig, D. (2014). CAMP Physio 21 Neurophysiology 1 2014
Power point presentation.

Koeppen, B.M., Stanton, B.A. (2012). Berne and Levy
Physiology, 6
th
ed. Molsby Inc., Elsevier Inc.

Waxman, S.G. (2013). Clinical Neuroanatomy, 27
th
ed. The
McGraw-Hill Companies, Inc., United States of America.

Authors Notes on the Subject Matter