Functions of Synapses & Neurotransmitter

Prof. Dr. Rashid Mahmood

Physiology
of Synapses
 Objectives (Basic Functions of Synapses)

At the end of this presentation you should be able to :

• Define and classify synapses
• Explain physiological structure of synapse
• Describe Mechanism by Which an Action Potential Causes Transmitter
Release from the Presynaptic Terminals
• Describe synaptic transmission and explain properties of synaptic
transmission.
• Describe mechanism of action of neurotransmitter on the post synaptic
membrane.
• Describe Second messenger system in the post synaptic neuron
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 Objectives (Neurotransmitters)
• Define the characteristics of a neurotransmitter
• Enumerate the neurotransmitters involved in central nervous
system.
• Classify neurotransmitters and describe the actions of some
common neurotransmitters in central nervous system.

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 Reviewing Terms and Facts
True/ False Questions (Pre-test)
• Conformational changes in channel proteins brought about by voltage
changes are responsible for opening and closing Na+ and K+ gates
during the generation of an action potential.True
• The Na+–K+ pump restores the membrane to resting potential after it
reaches the peak of an action potential. False
• After an action potential, the K+ concentration is greater outside the cell
than inside the cell because of the efflux of K+ during the falling phase.False
• Postsynaptic neurons can either excite or inhibit presynaptic neurons. False
• Second-messenger systems ultimately bring about the desired cell
response by inducing a change in the shape and function of particular
True
designated intracellular proteins.
5
Functions of Synapses & Neurotransmitter © Prof. Dr. Rashid Mahmood
 Thinking at a higher level
Which of the following would occur if a neuron were
experimentally stimulated simultaneously at both ends?
A. The action potentials would pass in the middle and travel to the
opposite ends.
B. The action potentials would meet in the middle and then be
propagated back to their starting positions.
C. The action potentials would stop as they met in the middle.
D. The stronger action potential would override the weaker action
potential.
E. Summation would occur when the action potentials met in the
middle, resulting in a larger action potential. 6
Functions of Synapses & Neurotransmitter © Prof. Dr. Rashid Mahmood
 Thinking at a higher level
Which of the following would occur if a neuron were experimentally stimulated simultaneously at both ends?
A. The action potentials would pass in the middle and travel to the opposite ends.
B. The action potentials would meet in the middle and then be propagated back to their starting positions.
C. The action potentials would stop as they met in the middle.
D. The stronger action potential would override the weaker action potential.
E. Summation would occur when the action potentials met in the middle, resulting in a larger action potential.

Answer: . C. The action potentials would stop as they met in the middle. As the two action potentials
moving toward each other both reached the middle of the axon, the two adjacent patches of membrane in
the middle would be in a refractory period, so further propagation of either action potential would be
impossible.

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 Lesson Contents
• Definition
• Types
• Physiological anatomy
• Synaptic Transmission
• Release of neurotransmitter
• Second Messenger System in the Postsynaptic Neuron(G-Proteins)
• Neurotransmitter Removal
• Post synaptic potentials
• Neurotransmitters
• Assessment questions 8
Functions of Synapses & Neurotransmitter © Prof. Dr. Rashid Mahmood
 The Synapse
• Junctional point between
two neurons
that
transmits impulse
from first to the
second Neuron.
(Junction between muscle+
neuron=
Synapse?)
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Prof. Dr. Rashid Mahmood
Q. 1
Label the
parts B-G
B. Axon Hillock
C. Synapse
D. Myelin Sheath
E. Axon
F. Soma

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 Classification

• Anatomical Classification
• (on the Basis of Communication )
1. Axo-Dendritic
2. Axo-Somatic
3. Axo-Axonic
4. Dendro-dendritic (amacrine cells in Eye)
• Physiological Classification:
• (According to Nature)
1. Electrical
2. Chemical
Autapse
A chemical or electrical synapse that forms when the axon of one neuron synapses onto dendrites of the
same neuron.
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Rashid Mahmood
Anatomical Classification

1. Axo-Dendritic
2. Axo-Somatic
3. Axo-Axonic
4. Dendro-
dendritic

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Functions of Synapses & Neurotransmitter © Prof. Dr. Rashid
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 Electrical Synapse

Gap Junctions in
Cardiac &
Smooth
Muscle (& some
parts of CNS)

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Chemical Synapses

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Prof. Dr. Rashid Mahmood
 Physiological Anatomy

Components
1. Presynaptic
terminal
f t
e
Cl
t ic 3. Postsynaptic
ap membrane
y n
Typical Anterior Motor
. S
Neuron 2
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Assessment
Q. 2:
Write 3
differences
between
chemical
synapse &
electrical
synapse
Answer in next slide
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 Answer Q. 2: Write 3 differences between
chemical synapse & electrical synapse

1. mode of transmission
2. physical junction not necessary in electrical synapse
3. two-way conduction possible in electrical synapse
Electrical and chemical synapses differ fundamentally in their transmission mechanisms.
A. At electrical synapses, gap junctions between pre- and postsynaptic membranes permit current to
flow passively through intercellular channels. This current flow changes the postsynaptic membrane
potential, initiating (or in some instances inhibiting) the generation of postsynaptic action
potentials.
B. At chemical synapses, there is no intercellular continuity, and thus no direct flow of current from
pre- to postsynaptic cell. Synaptic current flows across the postsynaptic membrane only in response
to the secretion of neurotransmitters which open or close postsynaptic ion channels after binding
to receptor molecules.
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 Synaptic Transmission
• Action Potential In Pre-synaptic Terminal
• Opening of Ca++ Channels in the Presynaptic
Membrane .

• Entry of Ca++ ions causes fusion of Vesicles &

release of Neuro- Transmitter into the synaptic
Cleft

• Binding of Neurotransmitter with receptors site

. Opening (or closing) of Ligand Gated Channels
• Excitation OR Inhibition
(Depending upon the type of
neurotransmitter released & receptor)

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 Release of neurotransmitter

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 Second Messenger System
in the Postsynaptic Neuron(G-Proteins)

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 Neurotransmitter Removal

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Rashid Mahmood Monoamine Oxidase 23
 Thinking at a higher level (Q.3)
• 3. Assume you touched a hot stove with your finger. Contraction of the biceps
muscle causes flexion (bending) of the elbow, whereas contraction of the
triceps muscle causes extension (straightening) of the elbow. What pattern of
postsynaptic potentials would you expect to be initiated as a reflex in the cell
bodies of the neurons controlling these muscles to pull your hand away from
the painful stimulus: excitatory postsynaptic potentials (EPSPs) or inhibitory
postsynaptic potentials (IPSPs)?

• Now assume your finger is being pricked to obtain a blood sample. The same
withdrawal reflex would be initiated. What pattern of postsynaptic potentials
would you voluntarily produce in the neurons controlling the biceps and
triceps to keep your arm extended despite the painful stimulus?
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 Thinking at a higher level (Answer to Q.3)
• Answer: 3. The hand could be pulled away from the hot stove by flexion of
the elbow accomplished by summation of EPSPs at the cell bodies of the
neurons controlling the biceps muscle, thus bringing these neurons to
threshold. The subsequent action potentials generated in these neurons
would stimulate contraction of the biceps. Simultaneous contraction of the
triceps muscle, which would oppose the desired flexion of the elbow, could be
prevented by generation of IPSPs at the cell bodies of the neurons controlling
this muscle. These IPSPs would keep the triceps neurons from reaching
threshold and firing so that the triceps would not be stimulated to contract.
The arm could deliberately be extended despite a painful finger prick by
voluntarily generating EPSPs to override the reflex IPSPs at the neuronal cell
bodies controlling the triceps while simultaneously generating IPSPs to
override the Functions
reflex EPSPs
of Synapses at the© Prof.
& Neurotransmitter neuronal cell bodies controlling the
Dr. Rashid Mahmood
25biceps.
 Post synaptic potentials

• EPSPs & IPSPs

• GPSP

• Summation of Excitation and Inhibition in Dendrites

• Spatial & Temporal summations

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 Post
Summation of postsynaptic potentials. (A) A
microelectrode records the postsynaptic potentials synaptic
produced by the activity of two excitatory synapses
(E1 and E2) and an inhibitory synapse (I). (B) Electrical
potentials
responses to synaptic activation. Stimulating either
excitatory synapse (E1 or E2) produces a subthreshold
EPSP, whereas stimulating both synapses at the same
time (E1 + E2) produces a suprathreshold EPSP that
evokes a postsynaptic action potential (shown in
blue). Activation of the inhibitory synapse alone (I)
results in a hyperpolarizing IPSP. Summing this IPSP
(dashed red line) with the EPSP (dashed yellow line)
produced by one excitatory synapse (E1 + I) reduces
the amplitude of the EPSP (orange line), while
summing it with the suprathreshold EPSP produced
by activating synapses E1 and E2 keeps the
postsynaptic neuro

Functions of Synapses & Neurotransmitter ©

Prof. Dr. Rashid Mahmood
Post synaptic potentials

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 Post synaptic potentials

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Post synaptic potentials

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Post synaptic potentials

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 Functions of Synapse depends on
• Synaptic polarization
• Neurotransmitter
• Types of synapses based on neurotransmitter released:
1. glutamatergic(often excitatory),
2. GABAergic (often inhibitory),
3. cholinergic (e.g. vertebrate neuromuscular junction), and
4. adrenergic (releasing norepinephrine)

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 Thinking at a higher level (Q.4)
• Assume presynaptic excitatory neuron A terminates on a
postsynaptic cell near the axon hillock and presynaptic
excitatory neuron B terminates on the same postsynaptic cell
on a dendrite located on the side of the cell body opposite
the axon hillock. Explain why rapid firing of presynaptic
neuron A could bring the postsynaptic neuron to threshold
through temporal summation, thus initiating an action
potential, whereas firing of presynaptic neuron B at the same
frequency and the same magnitude of EPSPs may not bring
the postsynaptic neuron to threshold
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 Thinking at a higher level (Answer to Q.4)
• An EPSP, being a graded potential, spreads decrementally from its site of initiation in
the postsynaptic neuron. If presynaptic neuron A (near the axon hillock of the
postsynaptic cell) and presynaptic neuron B (on the opposite side of the postsynaptic
cell body) both initiate EPSPs of the same magnitude and frequency, the EPSPs from A
are of greater strength when they reach the axon hillock than the EPSPs from B. An
EPSP from B decreases more in magnitude as it travels farther before reaching the axon
hillock, the region of lowest threshold and thus the site of action potential initiation.
Temporal summation of the larger EPSPs from A may bring the axon hillock to threshold
and initiate
• an action potential in the postsynaptic neuron, whereas temporal summation of the
weaker EPSPs from B at the axon hillock may not be sufficient to bring this region to
threshold. Thus, the proximity of a presynaptic neuron to the axon hillock can bias its
Functions of Synapses & Neurotransmitter © Prof. Dr. Rashid Mahmood

influence on the postsynaptic cell. 34

 Q.5, Reviewing Terms and Facts
True/ False Questions (Post-test)
A. Conformational changes in channel proteins brought about by voltage
changes are responsible for opening and closing Na+ and K+ gates
A. True
during the generation of an action potential.
B. The Na+–K+ pump restores the membrane to resting potential
B. False after it
reaches the peak of an action potential.
C. After an action potential, the K+ concentration is greater outside the cell
than inside the cell because of the efflux of K+ during C.theFalsefalling phase.

D. Postsynaptic neurons can either excite or inhibit presynaptic neurons.

E. Second-messenger systems ultimately bring about the desired cell
response by inducing a change in the shape and function of particular
E. True
designated intracellular proteins. D. False
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Answer: . C.Q.6
The action
Thinkingpotentials
atwould stop as they
a higher met in the middle. As the
level
two action potentials moving toward each other both reached the middle of the
axon, the two adjacent patches of membrane in the middle would be in a
Which of
refractory the following
period, would occur
so further propagation if a neuron
of either action were
potential would be
experimentally stimulated simultaneously at both ends?
impossible.
A. The action potentials would pass in the middle and travel to the
opposite ends.
B. The action potentials would meet in the middle and then be
propagated back to their starting positions.
C. The action potentials would stop as they met in the middle.
D. The stronger action potential would override the weaker action
potential.
E. Summation would occur when the action potentials met in the
middle, resulting in a larger action potential. 36
Functions of Synapses & Neurotransmitter © Prof. Dr. Rashid Mahmood
 Neurotransmitters
• Chemical Substances That Function as Synaptic Transmitters
• More than 50
• two groups
• small-molecule, rapidly acting
• large-molecule, Slowly acting (Neuropeptides/ Growth
Factors)

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 Small-molecule, rapidly acting
• Class I
• Acetylcholine
• Class II: The Amines
• Norepinephrine
• Epinephrine
• Dopamine
• Serotonin
• Histamine
• Class III: Amino Acids
• Gamma-aminobutyric acid (GABA)
• Glycine
• Glutamate
• Aspartate
• Class IV
•
Functions of Synapses & Neurotransmitter © Prof. Dr. Rashid Mahmood

Nitric oxide (NO) 38

Large-molecule, Slowly acting
• Pituitary peptides • Peptides that act on • Hypothalamic-
gut and brain releasing hormones
•
Adrenocorticotropic • Leucine enkephalin • Thyrotropin-
hormone (ACTH) releasing hormone
• Methionine
enkephalin • Luteinizing
• β-Endorphin
• Substance P hormone-releasing
• α-Melanocyte- hormone
stimulating • Gastrin
hormone • Somatostatin
• Cholecystokinin
(growth hormone
• Prolactin • Vasoactive intestinal inhibitory factor)
polypeptide (VIP)
• Luteinizing • From other tissues
hormone • Nerve growth factor
• Angiotensin II
• Thyrotropin • Brain-derived
neurotropic factor • Bradykinin
• Growth hormone • Neurotensin • Carnosine
• Vasopressin • Insulin • Sleep peptides
• Oxytocin • Glucagon
Functions of Synapses & Neurotransmitter © Prof. Dr. Rashid
• Calcitonin
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 Neurotransmitter (NT)

Receptor

Cell membrane Inside cell

(Post0synaptic)
(Cytoplasm/
(surface/ inside) Nucleus)

NT Complex (Change in function of cell)

Direct action Action on Genetic Machinery

Ion 1 2nd

channels_ Messenger
Linked System
receptors
7
G-Proteins- cAMP 5 Ca++-Calmodulin
Enzyme-
Linked 2 linked 3
Receptors Phspholipase C 6
receptors Protein synthesis

Activation of Functions 4
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"Second Messenger" System in the Postsynaptic
Neuron.

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Characteristics of Some of the More Important Small-Molecule
Transmitters

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 Acetylcholine
• Secreted by neurons in many areas of the nervous system but
specifically by
(1) the terminals of the large pyramidal cells from the motor cortex,
(2) several different types of neurons in the basal ganglia,
(3) the motor neurons that innervate the skeletal muscles,
(4) the preganglionic neurons of the autonomic nervous system,
(5) the postganglionic neurons of the parasympathetic nervous system, and
(6) some of the postganglionic neurons of the sympathetic nervous system.
• In most instances, acetylcholine has an excitatory effect; however, it
is known to have inhibitory effects at some peripheral
parasympathetic nerve endings, such as inhibition of the heart by the
vagus nerves. 43
Functions of Synapses & Neurotransmitter © Prof. Dr. Rashid Mahmood
 Norepinephrine
• Secreted by the terminals of many neurons whose cell bodies
are located in
• Most postganglionic neurons of the sympathetic nervous system
• brain stem and
• hypothalamus.
• Specifically, in the locus ceruleus in the pons send nerve fibers to widespread areas of the brain to
help control overall activity and mood of the mind, such as increasing the level of wakefulness.
• In most of these areas, norepinephrine probably activates
excitatory receptors, but in a few areas, it activates inhibitory
receptors instead.

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 Dopamine & Glycine
• Dopamine
• Secreted in the substantia nigra.
• Termination: mainly in the striatal region of the basal ganglia.
• Effect
• usually inhibition.

• Glycine:
• Secreted mainly in spinal cord.
• Effect:
• Probably always inhibition

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 GABA & Glutamate
• GABA (gamma-aminobutyric acid)
• Secreted in
• spinal cord,
• cerebellum,
• basal ganglia, and
• many areas of the cortex.
• Effect:
• Probably always inhibition

• Glutamate
• Secreted by
• many sensory pathways &
• many areas of the cerebral cortex.
• Effect: Functions of Synapses & Neurotransmitter © Prof. Dr. Rashid Mahmood
• Probably always causes excitation. 46
 Serotonin
• Secreted in
• median raphe of the brain stem
• Termination:
• many brain and spinal cord areas, especially to
• dorsal horns of the spinal cord and
• hypothalamus.

• Effects:
• Inhibitor of pain pathways in the cord,
• inhibitor action in the higher regions of the nervous system is
believed to help control the mood of the person, perhaps even to
cause sleep. 47
Functions of Synapses & Neurotransmitter © Prof. Dr. Rashid Mahmood
 Nitric Oxide
• Secreted by nerve terminals in areas of the brain responsible
for long-term behavior and for memory.
• Different mechanism of formation
• Not preformed and stored in vesicles in the presynaptic
terminal as are other transmitters. Instead, it is
synthesized almost instantly

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 See Also
• Active zone
• Autapse
• Exocytosis
• Immunological synapse
• Neurotransmitter vesicle
• Postsynaptic density
• Synaptopathy
• Roll in memory
• Synaptic adhesion molecules
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Properties of Synapses (Self-Study)
1. One
8. Way Conduction
Occlusion& Subliminal Fringe
9. Synaptic
2. Convergence
Delay
10. Divergence(EPSP)
3. Excitation
11. Recruitment
4. Inhibition
12. 1.
Afterdischarge
Presynaptic Inhibition
13. 2. Postsynaptic
Posttetanic Inhibition
Potentiation
3. Reciprocal Inhibition
14. Habituation
5. Synaptic fatigue
15. Effect of Acidosis & Alkalosis
6. Summation
16. Effect of Hypoxia on Synaptic Transmission
1. Spatial summation
17. 2.
Effect of Drugs
Temporal on Synaptic Transmission
summation
7. Facilitation
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Prof. Dr. Rashid Mahmood
 Summary

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 Learning Resources
• Guyton and Hall (Textbook of physiology), 14th Edition

• Lecture Notes Neurophysiology by Prof. Dr. Muhammad

Tariq 3rd Edition (Co-Author: Prof. Dr. Rashid Mahmood)

• Neurophysiology for Medical Students by Prof. Dr. Masood

Ahmed Khan 2nd Edition (Co-Author: Prof. Dr. Rashid
Mahmood)

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 Thank You

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Functions of Synapses &
Neurotransmitter-II

Prof. Dr. Rashid Mahmood

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