 Text.

 Important Lecture
 Formulas No.1
 Numbers
 Doctor notes ‫« وإن المالئكة لتضع أجنحتها‬
ً
 Extra notes and explanation » ‫لطالب العلم رضا بما يصنع‬

1
 Physiology of Synapses &Receptors

Objectives:
1. Define a synapse and describe the structure and function of chemical and electrical
synapses.
2. Define what neurotransmitters are, and how they are released and act on their receptors,
and
3. how they are removed.
4. Differentiate between ionotropic receptors and metabotropic receptors
5. Differentiate between postsynaptic and presynaptic inhibition, and between excitatory and
6. inhibitory postsynaptic potentials (EPSPs and IPSPs).
7. Describe properties of synapses and explain the nature of temporal and spatial
summation.
8. Appreciate that effectiveness of neurotransmitters can be modified by drugs and diseases.

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 ONLY IN MALES’ SLIDES

Synaptic transmission,
How brain functions? neurotransmitters
 Collection of sensory input. Information is transmitted in the central nervous system
 Central Integration. mainly in the form of nerve action potentials, called nerve
impulses, through a succession of neurons, one after another.
 Motor output.
Propagation of AP in the axon
will result in the opening of
voltage-gated Ca channels
 Calcium activates
calmodulin  calmodulin
activates protein kinase
 PK exposes syntaxin
and Synaptobrevin
causing the vesicle to
become “sticky”
vesicles fuse in docking
site and NTs are releases.

syntaxin and synaptobrevin are proteins found in the

membranes of synaptic vesicles. They play a role in vesicle fusion
to the “ docking “ site.

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 Structure of chemical
Synapse synapses
What is it? 1. Synaptic knob (presynaptic terminal):

ONLY IN FEMALES’
 It is a junction where the axon or some other portion of It has synaptic vesicles (neurotransmitter vesicles).
one cell (presynaptic cell)Terminates on the dendrites, soma, or
axon of another neuron (post synaptic cell).

SLIDES
 The CNS contains more than ONLY IN FEMALES’ SLIDES 2. Synaptic cleft (gap):
100 billion neurons. • The space between the axon terminal and sarcolemma
 The brain has 86 billion neurons. where neurotransmitters release into.
 Some CNS neurons receive 20,000 synapses.
• It has a width of 200-300 angstroms.
 Synaptic input is converted to a nerve impulse (ap) at the axon
hillock.
 The output signal (AP) travels by way of a single axon leaving th 3. Postsynaptic membrane:
e neuron.
It has receptors for neurotransmitters or ion channels.
 The synapse is present in the CNS. And the Junction is present
outside it.
 The brain only uses glucose for Energy.  Damage in Wernicke's area that is located on the union of
 Unlike muscles that can sustain no blood supply for 2 hours, parietal and occipital lobe will result in loss of
the brain can only last a few seconds before serious damage is comprehension. E.g. when asked about their name, patients
inflicted. will reply with something unrelated like “the weather is
cold”

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Synapse
ONLY IN MALES’ SLIDES ONLY IN FEMALES’ SLIDES

 A synapse is the connection between a neuron and a

Examples of Junctions outside
second cell.
the CNS
 In the CNS, this other cell is also a neuron.

 In the PNS, the other cell may be either a neuron or an

Contact between:
effector cell e.g. gland or muscle. autonomic neurons
Neuromuscular
and smooth, cardiac
junction muscles and any other
effector cells.

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 ONLY IN FEMALES’ SLIDES
Structure of
Synapse chemical synapses

6
 Functional anatomy: Types of synapses
Types of synapses

Anatomical types Functional types

Axodendiritic Axosomatic Other types Chemical synapses Electrical synapses conjoint synapses

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Anatomical types
Types of synapses

Anatomical types Functional types

Synapses between the axon of one neuron
Axodendiritic and the dendrite of another neuron. Chemical synapses

Axosomatic synapses between the axon of one neuron

and the soma of another neuron. Electrical synapses

Other types
axoaxonic: axon to axon.
conjoint synapses
dendrodendritic: dendrite to dendrite.

dendrosomatic: dendrites to soma.

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Functional types
Functional types
Chemical synapses Electrical synapses conjoint synapses
Via Neurotransmitters. Ion exchange via Gap Junctions. ONLY IN MALES’ SLIDES Both electrical and chemical.
20-30 nm. 2-4 nm.
One-direction ONLY IN MALES’ SLIDES Bi-direction transmission. ONLY IN MALES’ SLIDES
transmission.
‫ر‬
،‫انسمت الزم يرتبط بالمستقبل‬
‫ ألن النيوروتر‬،‫اإلتجاه واحد‬ .‫ ألن األيونات ال تتطلب مستقبل‬،‫بإتجاهي‬
.‫والمستقبل يكون يف البوست سينابتك فقط‬
Almost all synapses in the CNS. (Most common less common than Chemical synapses, and are very rare in the brain. Example: neurons in the lateral
type) vestibular nucleus
A neuron secretes a chemical ONLY IN FEMALES’ SLIDES • membrane of the pre and postsynaptic

ONLY IN FEMALES’ SLIDES

substance called neurons come close together.
neurotransmitter at • Gap junctions form.
the synapse to act on the • low membrane borders, which allows
next neuron (by binding to direct passage of ions and small molecules.
a specific receptor enabling • Correspond to gap junctions found in
an electrical signal other cell types
“postsynaptic potential or • if present, they are Important in the CNS in:
action potential”) to excite - Mental attention.
it, inhibit or modify its - Emotions & Memory.
sensitivity. - Arousal from sleep.

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 ONLY IN MALES’ SLIDES

Cont.
Functional types
Chemical synapses Electrical synapses
 Terminal bouton is separated from postsynaptic cell by Impulses can be regenerated without interruption in adjacent cells.
synaptic cleft. Gap junctions:
• Adjacent cells electrically coupled through a channel.
 NTs are released from synaptic vesicles. • Each gap junction is composed of 12 connexin proteins.
 The bidirectional transmission of electrical synapses
 Vesicles fuse with axon
permits them to help coordinate the activities of large
membrane and NT released by
groups of interconnected neurons.
exocytosis.
 Promotes synchronous firing of a group of interconnected
neurons.
 Amount of NTs released
For example in:
depends upon frequency of AP.
• Mental attention.
• Emotions and Memory
• Arousal from sleep
Examples: Smooth and cardiac muscles, brain, and glial cells.

• In the Electrical synapses there is a direct contact between pre synaptic and post synaptic.
• No delay occurs in Electrical synapses ( unlike chemical synapses).
• As you see in the picture, the space between pre synapse and post synapse in the chemical is larger than electrical.
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Recall
Recall what you studied in MSK block about neurotransmitters:

1 2 3
Increase ca2 concentration in
Lead to opening of ca2 channels and
Arrival of AP in the presynaptic. presynaptic which will lead to the
releasing of ca2 through vessels.
transmission to the postsynaptic.

5 4
Neurotransmitters will lead to the
Will reach to the threshold.
change of electrical grave in CM.

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 Extra

Synaptic Vesicle Synaptic vesicular membrane

 An abundant organelle with a diameter of 40 nm.  Synaptotagmin (protein on the vesicle involved in vesicle
fusion) helps the vesicle to bind to the terminal membrane
 Can accommodate only a limited number of neurotransmit
without Ca.
ters.

 Each vesicle contain only one type of neurotransmitters.  When Ca binds to synaptotagmin it starts the interaction
with SNARE proteins (on the presynaptic membrane)
 Different vesicles containing different NTs are often found causing exocytosis.
in a single synaptic knob.  Exocytosis occurs only in vesicles close to the terminal me
mbrane.
 There are over 100 Neurotransmitter.

 Synaptotagmin
and SNAREs are proteins
involved in the vesicle
fusion.

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Mechanism of a synaptic transmission
ONLY IN MALES’ SLIDES ONLY IN FEMALES’ SLIDES

1. NT release is rapid because many vesicles form fusion-

complexes at “docking site.”
2. AP travels down axon to bouton.
AP NT release
3. VG Ca2+ channels open.
4. Ca2+ enters bouton down concentration gradient.
5. Inward diffusion triggers rapid fusion of synaptic vesicles
and release of NTs. Inhibition or excitation
Binding to post
of the postsynaptic
6. Ca2+ activates calmodulin, which activates protein kinase. synaptic receptors
membrane
7. Protein kinase aid in the fusion of synaptic vesicles.
8. NTs are released and diffuse across synaptic cleft.  depending on the type of the neurotransmitter
9. NT (ligand) binds to specific receptor proteins in i.e. excitatory or inhibitory))
postsynaptic cell membrane.
10. NT effects are produced

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Fate of neurotransmitter
After a transmitter substance is released at a synapse, it must be removed by either:
 Diffusion out of synaptic cleft into surrounding fluid.
 Enzymatic destruction: e.g. Ach esterase for Ach.
 Active transport (reuptake) back into presynaptic terminal itself . e.g. Norepinephrine.

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 ONLY IN MALES’ SLIDES

Postsynaptic receptors
 Transmitter Substance acts on the Postsynaptic Neuron via “Receptor Proteins”.
 Have binding & intracellular component.

“Second Messenger” System in the

Postsynaptic Neuron acts in 4 Ways:
1. By gating ion channels directly and allowing
passage of specified types of ions through the
membrane (ionotropic receptors)
Receptor
activation
acts in
one of
2. By activating a “second messenger” that is not an
two ways: ion channel but a molecule that protrudes into the
cell cytoplasm and activates one or more
substances inside the postsynaptic neuron
(metabotropic receptors)

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 ONLY IN FEMALES’ SLIDES

Cont.
Components of postsynaptic
Receptors

Binding site Ionophore

That face the cleft to bind the ne It passes all the way through the
urotransmitter. membrane to interior.

2nd
Ion channels
messenger system

2nd messenger system in the postsynaptic membrane metabotropic (slow) receptors.

This mechanism is important where prolonged postsynaptic changes are needed to stays for days, months, years (memory). Next slide
Effects: intracellular enzymes activation, gene transcription, etc.

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 ONLY IN FEMALES’ SLIDES

Ion Channels
 Ion Channels Ionotropic (fast).
 (also known as ligandgated ion channels).
 Whether a NT is excitatory or inhibitory depends on the receptor it binds to:

Cation channels Anion channels

Mechanism Opening of Na+ channels → Increase Opening of Cl- channels → Decrease

membrane potential in positive direction membrane potential in negative direction
toward threshold level of excitation due to away from threshold level due to influx of
influx of (+)charges → (+) neuron. (-) charges → (-) neuron

Examples: Na+ (most common), K+, Ca++, … Cl- channels (mainly).

• The action of excitation and inhibition is depending on the charges.

• More positive = excitation.
• More negative = inhibition.

17
 Extra
Functional differences between ionotropic &
metabotropic receptors
IONOTROPIC METABOTROPIC
Mediate rapid PSPs. Mediate slower PSPs

Duration of PSPs is 10-30 ms or less Duration from 100`s ms to minutes or longer.

PSPs (EPSP or IPSP) develop within 1-2 msec after This slowness is due to activation of second
an AP reaching the presynaptic terminal messengers leading to opening of ion channels

A NT may activate both ionotropic and metabotropic receptors to produce both fast & slow
postsynaptic potentials at the same synapse

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 ONLY IN FEMALES’ SLIDES

Electrical events in postsynaptic neurons

Electrical events in postsynaptic neuron

1. Resting membrane potential

2. Excitatory postsynaptic potential (EPSPs) 3. Inhibitory postsynaptic potentials (IPSPs)
(RMP) of neuronal soma
• When excitatory neurotransmitter binds to its receptor on
post synaptic membrane → partial depolarization
(increase Na influx) of postsynaptic cell membrane Immediately
under presynaptic ending, i.e. EPSPs. How?
• Soma of a neuron has a RMP of • When an inhibitory NT binds to its receptor on post
• If this potential rises enough to threshold level → AP will synaptic membrane, it causes hyperpolarization of the
about -65 mv which is less negative
develop and excite the neuron. postsynaptic membrane
than the (-70 to 90) mv found in
skeletal muscles fibers. • This summation will cause the membrane potential to increase • Increases membrane permeability to Cl- of post
from -65 to -45 mV. (20 mV difference.) synaptic membrane (produced by inhibitory
• If the voltage is less negative → the neurotransmitter) →Decrease excitability and
neuron is excitable. • So the EPSPs = +20mV makes the membrane reach the firing membrane potential(more negative).Where the
level → AP develops at axon hillock. membrane reaches -70 mV (5 mV difference of the RMP.)

• Synapse on the cell body is more effective than other parts of

the neuron.

How EPSPs differs from Action potential?

• Proportionate to the strength of the stimulus.
• Can be summated.
• If large enough to reach firing level à AP is produced.
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 ONLY IN MALES’ SLIDES

EPSP & IPSP at Chemical Synapses

EPSP (excitatory postsynaptic potential): IPSP (inhibitory postsynaptic potential):

1. Opening of Na channels to threshold level

1. Opening of Cl- ion channels through the
(Most Common).
postsynaptic neuronal membrane.
2. ↓ conduction through Cl- or K channels, or both.
2. ↑ in conductance of K ions out of the Neuron.
3. Activation of receptor enzymes that inhibit
3.Various changes in the internal metabolism of the
cellular metabolic functions that ↑ inhibitory
postsynaptic neuron to excite or, in some instances,
membrane receptors or ↓ excitatory membrane
to ↑ excitatory membrane receptors or ↓ inhibitory
receptors.
membrane receptors.

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 Synaptic properties
Synaptic properties

1. One way conduction 2. Synaptic delay 3. Fatigue (synaptic depression)

It is due to exhaustion of neurotransmitter.

Synapses generally permit conduction
of impulses in one way How?
 It is the minimum time required for transmission across the s
i.e. from presynaptic to ynapse. If the presynaptic neurons are continuously
postsynaptic neuron. “Bell- Magendie  It is 0.5 ms for transmission across one synapse. Stimulated there may be an exhaustion of the
law”. neurotransmitter, (results in) →​ stoppage of
 This time is taken by: Synaptic transmission.
1. Discharge of transmitter substance by presynaptic terminal.
2. Diffusion of transmitter to postsynaptic membrane.
3. Action of transmitter on its receptor. In the pre synaptic membrane all of the
4. Action of transmitter to increase membrane permeability neurotransmitters used from continuous
5. Increased diffusion of Na+ to increase postsynaptic potential. stimulation will result in the arrival of ap but it
won't propagate.
• Clinical Importance: is that ONLY IN MALES’ SLIDES
we can know number of synapses involved in neuronal pathways
Synaptic fatigue is a protective phenomena.
by time lag.

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 ONLY IN MALES’ SLIDES

Cont. Fatigue (synaptic depression)

 The cause of this sudden cessation of reverberation is fatigue of synaptic junctions in the circuit. Fatigue beyond a certain
critical level lowers the stimulation of the next neuron in the circuit below threshold level so that the circuit feedback is
suddenly broken.

 Synaptic fatigue short-term (synaptic depression), is an activity dependent form of short term synaptic plasticity that results in
the temporary inability of neurons to fire and therefore transmit an
input signal.

 Almost these exact patterns of output signals are recorded from the
motor nerves exciting a muscle involved in a flexor reflex after pain
stimulation of the foot.

22
 Cont.
Synaptic properties

4. Convergence & Divergence 5. SYNAPTIC INHIBITION 6. Summation

Next slide.
Convergence Divergence Spatial Temporal

ONLY IN FEMALES’

ONLY IN FEMALES’
Axons of presynaptic Eliciting an action
When many presynapti When the frequency of
neurons devide into potential in a neuron

SLIDES

SLIDES
c neurons Converge stimulation increased
many branches that with input from
on anysingle postsynapti from the same
diverge to end on many multiple presynaptic
c neuron presynaptic fiver
postsynaptic neurons cells.

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 ONLY IN MALES’ SLIDES

Cont. (Summation)
Transmission of signals of different
intensity in nerve tracts

Spatial Temporal

Increasing signal Transmitting signals of

strength is transmitted increasing strength is by
by using progressively increasing the
greater numbers of frequency of nerve
fibers. impulses in each fiber

24
Synaptic Inhibition
6. Synaptic inhibition
Types Definition
A. Direct Inhibition (postsynaptic inhibition) Occurs when: An inhibitory neuron (releasing inhibitory substance) acts on a postsynaptic
neuron leading to hyperpolarization due to opening of Cl- [IPSPs] and/or K+ channels.
‫ر‬
.‫ ال يوجد وسيط أو تدخل‬،‫مباش‬ Example: Glycine at the level of the spinal cord to block pain impulses.
Occurs when: An inhibitory synaptic knob lies directly on
B. Indirect Inhibition (Presynaptic inhibition) the termination of a presynaptic excitatory fiber.
The inhibitory synaptic knob release a transmitter which inhibits the release of excitatory
َّ ‫غت ر‬
.‫ تطلب تدخل بري سينابتك وبوست سينابتيك‬،‫مباش‬ transmitter from the presynaptic fiber.
Example: GABA (Pain modification)
Inhibition of antagonist activity is initiated in the agonist muscle when agonist is excited.
C. Reciprocal Inhibition
ONLY IN FEMALES’ SLIDES
impulses pass directly to the motor neurons supplying the
same muscle and via branches to inhibitory interneurons that end on motor neurons of
antagonist muscle.

When flexing the arm, flexors are activated while extensor muscles are inhibited.
Negative feedback inhibitory interneuron of a spinal motor neuron.
D. Inhibitory Interneuron (Renshaw cells) Control the strength of contraction.
Renshaw cells have the same function as Reciprocal inhibition.

25 • Dopamine can be excitatory or inhibitory ( depending on the receptor ). However, glycine is always Inhibitory
Cont. Synaptic Inhibition:
Inhibitory interneuron ( Renshaw cells)
ONLY IN MALES’ SLIDES ONLY IN FEMALES’ SLIDES

26
 ONLY IN MALES’ SLIDES
Cont. Synaptic Inhibition:
Pre-synaptic inhibition
 Neuronal Circuit With Both Excitatory and Inhibitory Output Signals.
 This type of circuit is characteristic for controlling all antagonistic pairs of muscles, and it is called the reciprocal inhibition
circuit.

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 ONLY IN MALES’ SLIDES

Reverberatory (Oscillatory) Circuit

 Cause of Signal Prolongation. caused by positive feedback within the
neuronal that re-excite the input of the same circuit. Once stimulated, the
circuit may discharge repetitively for a long time called long term
potentiation

 The simplest Fig A, involves single neuron.

 Fig B shows additional neurons in the feedback circuit, which causes a longer
delay between initial discharge and the feedback signal.

 Fig C shows a more complex system in which both facilitatory and

inhibitory fibers impinge on the reverberating circuit.

 Fig D shows reverberating pathways with parallel fibers.

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 ONLY IN MALES’ SLIDES

Zones of neuronal pool

 The neuronal area stimulated by each incoming nerve fiber is called its
stimulatory field. Large numbers of the terminals from each input fiber lie
on the nearest neuron in its “field,” & fewer terminals lie on the neurons
farther away.

 Discharge zone of the incoming fiber, also called the excited zone (a with
suprathreshold stimulus).

 To each side, the neurons are facilitated but not excited, and these areas
are called the facilitated zone, also •called the subthreshold zone or
subliminal zone. (b & c not enough to cause excitation).

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 ONLY IN MALES’ SLIDES

Divergence.
In divergence weak signals entering a
neuronal pool are amplified. Two major types

Divergence into
Amplifying type
multiple tracts

Eg: dorsal columns: of

the spinal cord takes
two courses in the
lower part of the brain:
Eg: corticospinal 1. into the cerebellum.
pathway
2. on through the lower
regions of the brain to
the thalamus and
cerebral cortex.

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 ONLY IN MALES’ SLIDES

Convergence.
Convergence means signals from multiple inputs uniting to excite a single neuron

Action potentials converging on the neuron from multiple terminals provide enough
spatial summation to bring the neuron to the threshold required for discharge.

Convergence can also result from input signals (excitatory or inhibitory) from
multiple sources: the interneurons of the spinal cord receive converging
signals from:
1. peripheral nerve fibers entering the cord.
2. Propriospinal fibers passing from one segment of the
cord to another.
3. corticospinal fibers from the cerebral cortex.
4. several other long pathways descending from the
brain into the spinal cord.
From interneurons converge on the anterior motor
neurons to control muscle function. By summation

31
Doctor’s notes
Reciprocal Inhibition: Inhibitory Interneuron (Renshaw cells):
 Because the sensory will travel and at the level of the spinal cord,  It receives collateral information from the motor.
sensory information about the pain that we are experiencing will
travel and give information to the motor component for the motor
reaction and it will give responses to contract this muscle and to  That means when sensory information is received and the muscle
inhibit the antagonist and withdrawal will occur. gets contracted., the collateral and interneuron will receive the
information from the motor through this collateral fibers to be
informed about the muscle contraction because it will control the
 Reciprocal antagonists are opposite each other. The type of action muscle contraction.
with inhibition of the opposite action
.‫مثل لما يحدث عندنا ألم بسيط وظيفة النتتنيورونز أنها تمنع زيادة اإلنقباض يف العضالت‬

 It receives collateral information from the motor.

 That means when sensory information is received and the muscle

gets contracted, the collateral and interneuron will receive the
information from the motor through this collateral fibers to be
informed about the muscle contraction because it will control the
muscle contraction.
‫كنتول يصت ر‬
‫مباشة‬ ‫ من غت تفكت أو ر‬،‫مثل لما ننجرح باإلبرة ما نجلس نقرر إذا هو يؤلمنا أو ال‬
‫والشعور المؤلم يتوزع عىل الكثت من السيجمينتس من السباينل كورد عشان تعطينا الكثت‬
.‫كونتاكشي وانهيبيشن اكشت‬ ‫من المسل ر‬

32
Factors affecting synaptic transmission
1. Alkalosis: 3. Hypoxia:
 Increases neuronal excitability.  Causes Depression of neurons.
 Causes cerebral epileptic seizures (due to Increased excitability of
cerebral neurons).
 Example: over breathing in a person with epilepsy.
4. Drugs:
The over breathing blows off carbon dioxide and therefore  Caffeine found in coffee, tea, strychnine, theophylline and
elevates the pH of the blood momentarily. theobromine increases neuronal excitability, by reducing the
threshold for excitation of neurons.

2. Acidosis:
 Depresses neuronal activity.
 pH around 7 “As in severe diabetic or uremic acidosis” usually
causes a coma.

33
 Thank you!

.‫ اعمل و أنت تعلم أن هللا ال يضيع أجر من أحسن عمال‬،‫ اعمل لتمسح دمعة‬،‫اعمل لترسم بسمة‬

The Physiology 436 Team: Team Leaders:

Lulwah Alshiha
Females Members: Males Members:
Amal AlQarni Qaiss Almuhaideb Laila Mathkour
Ghada Almazrou Mohammad Alayed

Contact us:

References:
• Females and Males slides.
• Guyton and Hall Textbook of Medical Physiology (Thirteenth Edition.)

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