Lecture 9:

Neurophysiology
Part Two

Neurophysiology: Part 2
• Neurophysiology
– Nervous System Overview
– Electrical Communication in Neurons
– Chemical Communication in Neurons
– Nervous System Pathways

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 Neuron Communication
• Neurons communicate electrically through electrical
gradients and chemically through neurotransmitters
• electrical communication: movement of ions in an out of cell
membranes
• can be small, local or travel long distances down the branches of the
cell

• chemical communication: release of neurotransmitters

(ligand) to nearby neurotransmitter receptors (receptor) at
synapses

1) Input zone receives incoming

signals from other neurons.
Dendrites

Cell body
2) Trigger zone
initiates action 3) Conducting zone conducts
potentials. action potentials in undiminishing
Nucleus fashion, often over long distances.
Axon hillock
Axon (may be from 1mm
to more than 1 m long)

Axon
terminals
Dendrites 4) Output zone releases
neurotransmitter that
Cell body influences other cells.

Axon

Fig. 4-8, p. 98

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 Synapses 1. Synapses with another neuron

• Synapses are Neuron

connection points Neuron

between two
neurons or 2. Neuromuscular synapses
between a neuron Neuromuscular synapses

and a muscle, Neuron

gland, or cell

Skeletal
muscle

3. Neuroglandular synapses

Neuroglandular
Neuron synapses

Gland cells

Neuron Communication
• At the connection between two neurons there is a space
(syaptic cleft) that does not allow electrical current to flow,
so a chemical signal is required as an intermediate.
• Communication between two neurons is always:
– ELECTRICAL: action potential in 1st (pre-synaptic) cell
– CHEMICAL: neurotransmitter released to cross synapse
– ELECTRICAL: graded or action potential in 2nd (post-synaptic) cell

3
 Synapses Presynaptic neuron

Structures of a Synapse:
• Presynaptic neuron
• Synaptic cleft
• Postsynaptic neuron Synapse

Postsynaptic neurons

Axon Terminal

Synaptic vesicles
Presynaptic membrane
Synaptic cleft

Postsynaptic membrane

Presynaptic
Neuron Presynaptic neuron

• Presynaptic neuron: the

neuron that is
transmitting a signal TO
the synapse
– Synaptic Vesicles: tiny sacs Synapse
of chemicals that will be
Postsynaptic neurons
released when the signal
reaches the axon terminal
– Neurotransmitters:
chemicals found in
synaptic vesicles that will
excite the postsynaptic Axon Terminal

neuron, muscle, or gland Synaptic vesicles

cell. Presynaptic membrane
Synaptic cleft

Postsynaptic membrane

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 Synaptic Cleft Presynaptic neuron

• Synaptic Cleft: the space

between the axon
terminal and the
postsynaptic cell
• electrical signals cannot Synapse

directly pass here, but Postsynaptic neurons

chemicals CAN

Axon Terminal

Synaptic vesicles
Presynaptic membrane
Synaptic cleft

Postsynaptic membrane

Postsynaptic
Neuron Presynaptic neuron

• Postsynaptic neuron: the

neuron that is receiving
the signal FROM the
synapse
– Neurotransmitter Synapse
Receptors: proteins found
Postsynaptic neurons
in the postsynaptic cell
membrane that bind to
chemical
neurotransmitters
– Ion channels: proteins in
the postsynaptic cell Axon Terminal

membrane that open to Synaptic vesicles

allow electrical impulses Presynaptic membrane
to conduct through the Synaptic cleft
membrane
Postsynaptic membrane

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5
 Synapse
A synapse contains specialized structures to transmit electrical
and chemical signals

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Events at the Synapse

Pre-synaptic events at the axon terminal:
1. ACTION POTENTIAL
2. Ca2+ ENTRY
3. NT RELEASE
Post-synaptic events at the dendrite:
4. NT RECEPTOR ACTIVATION
5. IONS ENTER
6. GRADED POTENTIAL

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6
 1. Action Potential Reaches Axon Terminal
After traveling through the pre-synaptic axon, the axon potential
reaches the presynaptic axon terminal
This depends solely on electrical conduction through the axon.
1

Axon of
presynaptic
neuron

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2. Calcium enters the Axon Terminal

Voltage gated Ca2+ channels are present in the axon terminal.
When the action potential enters, voltage gated Ca2+ channels
open and calcium enters the axon terminal

Voltage-gated
Ca2+ channel

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7
 3. Neurotransmitter Release
Vesicles filled with neurotransmitter, called synaptic vesicles are
in the axon terminal.
Ca2+ entry into the pre-synaptic terminal is the signal that causes
exocytosis of these vesicles and release of neurotransmitter
at the axon terminal

Synaptic
vesicle

Synaptic
vesicle

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4. Neurotransmitter Receptor Activation

Neurotransmitter diffuses across the synaptic cleft and binds to
neurotransmitter receptors on the post-synaptic cell
membrane

Receptor for Receptor for

neurotransmitter neurotransmitter

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 5. Ion Channels open on Post-Synaptic cell
Neurotransmitter binding to its receptor causes the opening of
ion channels attached to the receptor. Ions move into the
post-synaptic cell membrane

Receptor for Receptor for

neurotransmitter neurotransmitter

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6. Graded Potential at Dendrite

Influx of ions into the post-synaptic cell will cause a graded
potential at the dendrite of the post-synaptic cell.

Postsynaptic dendrite

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 Summary Events at the Synapse
1. ACTION POTENTIAL PRE-SYNAPTIC: axon potential reaches
the presynaptic axon terminal
2. Ca2+ ENTRY PRE-SYNAPTIC: Voltage gated Ca2+ channels in the
axon terminal open in response to the action potential, Ca2+
enters the axon terminal
3. NT RELEASE: Ca2+ causes release of neurotransmitter via
exocytosis at the axon terminal
4. NT RECEPTOR ACTIVATION: neurotranmitter binds to
neurotransmitter receptors on the post-synaptic membrane
5. IONS ENTER POST-SYNAPTIC: neurotransmitter receptor
activation opens ion channels in the post-synaptic membrane
6. GRADED POTENTIAL in the post-synaptic cell dendrite (can
lead to ACTION POTENTIALS)

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Summary Events at the Synapse

1
Axon of
presynaptic
neuron

Voltage-gated
Ca2+ channel Synaptic knob 3
Ca2+ (presynaptic
axon terminal)
2
Synaptic
Neuro- vesicle
transmitter
molecule Synaptic
3 cleft
Subsynaptic 4
membrane
5
4
Chemically gated
receptor-channel
for Na+, K+, or Cl– Receptor for
neurotransmitter 5 Postsynaptic neuron

Fig. 4-15, p. 108

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10
 Axon terminal
of presynaptic
neuron

Dendrite of
postsynaptic
neuron

Synaptic Synaptic
vesicles cleft

Fig. 4-15, p. 108

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EPSPs and IPSPs

The graded potential in the post-synaptic cell caused by synaptic
transmission is called a post-synaptic potential (PSP).
– EPSP: excitatory post-synaptic potential
• If the ion channel opens and positive ions flow IN to the post-
synaptic membrane (ex: Na+), it is excitatory (EPSP) to the cell
• used to increase depolarization, can lead to action potentials
– IPSP: inhibitory post-synaptic potential
• If negative ions flow IN to the post-synaptic membrane (ex: Cl-), it
is inhibitory (IPSP) to the cell
• used to hyperpolarize and reduce the number of action potentials

• The type of ion channel (Na+, Cl-, etc) activated by the

neurotransmitter will depend both on the neurotransmitter
and the neurotransmitter receptor type.

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11
 +30
Membrane potential (mV)
in postsynaptic neuron
0

Activation of synapse
Threshold
–50
potential
EPSP
–70

5 15 25 35 45
Time (msec)
(a) Excitatory synapse
Fig. 4-16a, p. 110

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Membrane potential (mV)

+30
in postsynaptic neuron

Activation of synapse
Threshold
–50
potential
–70
IPSP

5 15 25 35 45
Time (msec)
(b) Inhibitory synapse Fig. 4-16b, p. 110

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 Reaching Threshold (post-synaptic)
Dendrites Synaptic inputs
There are many inputs to (presynaptic axon terminals)

one neuron. EPSPs and

IPSPs will enter from
multiple synapses, their
combination of activity
will determine whether a
cell will reach threshold
for an action potential

– Resting potential = -70mV

– Threshold = -50 to -55 mV
Cell body of Axon Myelinated
– Graded potentials (EPSPs postsynaptic neuron hillock axon
and IPSPs) = +/- 10 mV

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Summation
• A single EPSP cannot induce an
action potential but they can be
summed
• The axon hillock keeps score of all
graded potentials received at the
dendrites

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 Summation of EPSPs and IPSPs
Graded potentials (EPSPs, IPSPs) are not subject to refractory periods
and can add up to create action potentials. There are two main
ways this can happen:

1. Temporal Summation: one pre-synaptic cell can cause EPSPs very

close in time, they will add up to threshold

2. Spatial Summation: two different pre-synaptic cells at different

locations can cause EPSPs at the same time, they will add up to
threshold.

* note IPSPs can also combine, but they will reduce the likelihood of
reaching threshold

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Temporal Summation
• Temporal summation –
one presynaptic neuron
increases the frequency of
impulses and more
neurotransmitters are
released in quick
succession
• same location, stimulation
increases timing

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14
 Spatial Summation
• Spatial summation – postsynaptic neuron is stimulated
by multiple presynaptic neurons at the same time
• same timing, stimulation increases locations
– IPSPs and EPSPs can also be summed and cancel each other out

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Summation of EPSPs and IPSPs

Excitatory
presynaptic inputs
Postsynaptic membrane potential (mV)

(a) No (b) Temporal (c) Spatial (d) EPSP-IPSP

summation summation summation cancellation

+30
Membrane
potential 0
recorded

Threshold
–50
Postsynaptic potential
cell –70 Resting
potential

Inhibitory
presynaptic input Time (msec)

Fig. 4-17, p. 111

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15
 Neurotransmitters
There are many types of neurotransmitters in the Nervous System. In
general, one neuron type releases one type of neurotransmitter. But, any
given neuron can respond to several types of neurotransmitters.
Some common examples:
– Acetylcholine
• found at neuromuscular synapses, autonomic nervous system
– Glutamate
• the main excitatory neurotransmitter in the brain
– GABA
• the main inhibitory neurotransmitter in the brain
– Norepinephrine
• autonomic nervous system, learning, emotion, behavioral pathways
– Dopamine
• learning, emotion, behavioral pathways
– Serotonin
• learning, emotion, behavioral pathways”

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Classification of Neurotransmitters by
Chemical Structure

• Acetylcholine (ACh)
• Biogenic amines – catecholamines, serotonin
• Amino acids – glutamate, glycine, GABA
• Peptides – endorphins, substance P
• Chemical Messengers: ATP and dissolved gases NO

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 Classification by Neurotransmitter Function

• Excitatory neurotransmitters (e.g., glutamate) cause

depolarization of post-synaptic neurons
• Inhibitory neurotransmitters (e.g., GABA and glycine) cause
hyperpolarization of post-synaptic neurons
• Some neurotransmitters can have BOTH excitatory and
inhibitory effects
– Determined by the receptor type of the postsynaptic
neuron
– Example: acetylcholine
• Excitatory at neuromuscular junctions with skeletal
muscle (nicotinic receptor)
• Inhibitory in cardiac muscle (muscarinic receptor)

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Neurotransmitter Receptor Mechanisms

• Direct: neurotransmitters that open ion channels
– Promote rapid responses “fast synapses”
– Examples: ACh and amino acids

34

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 Neurotransmitter Receptor Mechanisms

• Indirect: neurotransmitters that act through second messengers

– Promote long-lasting effects, “slow synapses”
– Examples: biogenic amines, peptides, and dissolved gases

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Effects of Neurotransmitters
• Neurotransmitter receptors mediate changes in membrane
potential according to:
– The amount of neurotransmitter released
– The amount of time the neurotransmitter is bound to
receptors
• Neurotransmitters will affect the membrane potential as long
as they are bound so they must be deactivated

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 Deactivation of Neurotransmitter Effects
Graded potentials will continue as long as the neurotransmitter is
bound to its receptor. So, the neurotransmitter must be
inactivated or removed in order to stop the graded potential.

1) Active Transport: neurotransmitter will be actively pumped

back into the pre-synaptic cell or nearby neuroglia
2) Enzymes: enzymes are present in the synaptic cleft that will
breakdown the neurotransmitter to quickly stop the signal
• ex: acetylcholinesterase
3) Diffusion: the neurotransmitter diffuses enough away from
the synaptic cleft to reduce its signal

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Deactivation of Neurotransmitters

38

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 Acetylcholine Related Enzymes
• Acetylcholinesterase is an enzyme found in the synaptic cleft that
degrades acetylcholine.
• Chemical Reaction:
AchE
acetylcholine à acetate + choline

• Choline is then actively transported back into the presynaptic

terminal and used to reform acetylcholine with the help of the
enzyme ChAT (choline acetyl transferase)
• Chemical reaction:
choline + AcetylCoA à acetylcholine
ChAT

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 Targets of Drugs & Disease
Many drugs alter synaptic activity.
Possible drug actions:
1) altering synthesis, storage or release of neurotransmitters
2) modifying neurotransmitter interaction with its receptor
3) influencing neurotransmitter reuptake or destruction
4) replacing deficient neurotransmitter with a substitute neurotransmitter

examples:
SSRI’s: selective serotonin reuptake inhibitors, prevent the reuptake of
serotonin, increasing the length of time that serotonin is at the synapse;
used to treat depression.
Tetanus Toxin: prevents release of GABA from inhibitory neurons at
neuromuscular synapses, causes uncontrolled muscle spasms (too much
excitation) and lock jaw.

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Neuron Communication
• Neurons communicate electrically through electrical
gradients and chemically through neurotransmitters
• electrical communication: movement of ions in an out of cell
membranes
• can be small, local or travel long distances down the branches of the
cell
• EPSPs, IPSPs, Action Potentials
• chemical communication: release of neurotransmitters
(ligand) to nearby neurotransmitter receptors (receptor) at
synapses
• effect on post-synaptic cell will depend on the neurotransmitter and
the receptor/ion channel interaction

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21
 Nervous System Pathways
The Nervous System overall is organized into complex pathways of multiple
cellular connections. Understanding the Nervous System requires an
understanding of how groups of multiple cells interact as Neural Circuits
For perspective:
• There are over 100 billion neurons in the nervous system, with over 1014
(100 quadrillion) synapses
• Any given neuron can be connected to 5,000 to 10,000 other neurons
• Modern computers cannot come close to the recognition, processing, and
learning that our Nervous System is capable of

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Convergent Pathways
A single cell is influenced by thousands of other cells, this is input converging
on one cell, and is a Convergent Pathway.

Postsynaptic
neuron

Presynaptic
inputs

Convergence of input
(one cell is influenced
by many others)
Fig. 4-19, p. 116

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 Divergent Pathways
A single cell can also branch to thousands of other cells, this is input
expanding from one cell to many and is a Divergent Pathway.

Presynaptic
inputs

Postsynaptic
neurons

Divergence of output
(one cell influences
many others)
Fig. 4-19, p. 116

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Information Coding in Neural Circuits

Ultimately, the information conveyed within a neural circuit is found within
the pattern of electrical stimulation

Graded Potential Patterns: subthreshold electrical EPSPs and IPSPs

• increase amplitude and frequency of EPSPs and IPSPs signals that more
activation has occurred

Action Potential Patterns: All or None electrical propogation

• CANNOT change the shape or amplitude of the AP
• increased frequency or change in pattern of AP’s is used as the “coding”
signal that activation has changed

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