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 Physiology - CNS

The Nervous System

- It is the major controling, regulatory, and communicating
system in the body.
- With endocrine systems, they maintain homeostasis
Functions:
1. sensory input
2. information processing
3. motor output

Organization of the nervous system

Central nervous system Peripheral nervous system

Componant the brain and spinal cord. peripheral nerves

- Integration of the input signals

function
- production of output signals.
Three major levels of the CNS: Subdivided into
a. Spinal cord level: a. Sensory Division: (Afferent Division)
- Immediate automatic activities such Consists of the receptors, axons and
as withdrawal reflexes and cell bodies of sensory neurons
evacuation of bladder and rectum.
b. Lower Brain Level: b. Motor Division: (Efferent Division):
- Control of subconscious activities of is further subdivided into:
levels the body, e.g. cardiovascular and • Somatic division: consists of the
respiratory functions axons of motor neurons that
- Maintenance of posture and innervate skeletal muscles.
equilibrium and emotional reactions.
c. Higher Brain or Cortical Level: • Autonomic division: consists of
- Control of motor and sensory the axons of motor neurons that
functions innervate the viscera, smooth
- Control of other higher functions muscles, cardiac muscles and
: thinking, learning, memory, and glands.
speech.

Dr. Elsherif 1
 Physiology - CNS

synaptic transmission

Synaptic transmission is the foundation of neural communication and information processing in

the nervous system. By transmitting impulses from one neuron to another
Definition of synapse:
- Is a junction between an axon terminal of one neuron (presynaptic neuron) and a second
neuron (post synaptic neuron).
- On average, each neuron has anywhere between a few to hundreds of thousands of synaptic
connections.
Types of synapses:

Chemical Synapse Electrical Synapse

Neurotransmitter release from Direct passage of electric current via low-

presynaptic neuron to act on receptors of resistance gap junctions.
the postsynaptic neuron.

Most common type in the human nervous Rare; found in specific areas like the retina and
system. olfactory bulb.

Slower due to chemical diffusion and Faster due to direct electrical communication.
receptor binding.

Function of Synaps:

a. Facilitating transmission from one neuron to the next.

b. Blocking transmission from one neuron to the next.
c. Amplification of weak impulses.
d. Distribution of impulses to many directions.
e. Changing a single impulse to repetitive impulses.
f. Integration between different types of neurons. g.
Storage of information, i.e. memory

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 Physiology - CNS

N.B.
A synape:-
• is not simple jumping of an action potential.
• is a complex process that permits grading and adjustment of neural activity
necessary for integration, interpretation and processing of information at different
levels of the CNS
• is a dynamic structure, increasing and decreasing in complexity and
number with use and experience.

Anatomy of synapses:

1. Presynaptic Axon Terminal (Synaptic Knob)

contains
a. Mitochondria: Provide ATP for synthesizing and releasing neurotransmitters.
b. Synaptic Vesicles:
• Small Clear Vesicles: Contain rapidly acting neurotransmitters (e.g., acetylcholine, glycine,
glutamate, GABA).
• Small Granular Vesicles: Contain catecholamines (e.g., dopamine, norepinephrine).
• Large Granular Vesicles: Contain slowly acting neuropeptides.

Vesicles release neurotransmitters at active zones on the presynaptic membrane.

c. SNARE Proteins:
• V-SNARE (Synaptobrevin): Located on the synaptic vesicle.
• T-SNARE (Syntaxin): Located on the presynaptic membrane.
• Function: Facilitate the fusion of vesicles with the membrane for neurotransmitter release.

2. Synaptic Cleft
• Structure: A 30-50 nm space between the presynaptic and postsynaptic neurons.
• Content: Filled with extracellular fluid rich in Nat, Cl, and poor in K*.

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 Physiology - CNS

3. Postsynaptic Membrane (PSM)

Contains receptors

a. Ionotropic Receptors: b. Metabotropic Receptors:

Part of ligand- gated ion channels Coupled to G proteins

directly affect neuronal activity. Separates pre- and

indirectly postsynaptic
affect neurons;
neuronal activity by allows
diffusion
modulating of neurotransmitters.
intracellular signaling pathways.

• Cation Channels: e.g., Na+, K+ or Separates pre- andFunctions:

postsynaptic neurons; allows

Ca2+ channels. diffusion

1. Open of neurotransmitters.
or close specific ion channels.

• Anion Channels: e.g., Cl channels. 2. Activate or inactivate enzymes (e.g., protein kinases).
3. Activate gene transcription to form new protein,
within the neuron.

Summary

presynaptic axonal
synaptic cleft postsynaptic membrane
terminal
Mitochondria, Synaptic 30-50 nm space with Ionotropic & Metabotropic
Structure
Vesicles, SNARE Protiens extracellular fluid Receptors

Synthesizes and releases Separates pre- and Separates

Receives pre- and
neurotransmitters
neurotransmitters into the postsynaptic neurons; allows postsynaptic neurons; allows
and initiates responses in the

synaptic cleft diffusion of diffusion

postsynaptic of either
neuron,
Function
neurotransmitters. neurotransmitters.
through direct ion channel
activation or indirect by
signalling pathway

Mechanism of Synaptic Transmission

1. Release of Chemical Transmitter
• Action Potential Arrival: Triggers opening of voltage-gated Ca2+ channels at the
presynaptic terminal.
• Calcium Influx: Ca2+ enters, leading to the fusion of synaptic vesicles with the presynaptic
membrane.
• Neurotransmitter Release: Vesicles release neurotransmitters into the synaptic cleft
proportional to Ca2+ influx.

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 Physiology - CNS

2. Binding to Receptors
• Neurotransmitters bind to specific receptors on the postsynaptic membrane, altering its ion
permeability.
3. Generation of Postsynaptic Potential
• Excitatory (EPSP): Membrane becomes less negative.
• Inhibitory (IPSP): Membrane becomes more negative.
• Both are graded potentials based on neurotransmitter quantity.
4. Removal of Neurotransmitters
• Enzymatic Inactivation: E.g., acetylcholine breakdown.
• Reuptake: E.g. catecholamines.
• Diffusion Away: E.g., neuropeptides.

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 Physiology - CNS

Types of Synaptic potential

A) Postsynaptic potential:

1. Excitatory postsynaptic potentials 2. Inhibitory Postsynaptic Potential

(EPSP) (IPSP)

local transient slate of partial local transient state of hyperpolarization of

Definition depolarization of postsynaptic postsynaptic membrane.
of postsynaptic membrane.
membrane.

• Release of excitatory neurotransmitter • Release of inhibitory neurotransmitter will

and binding to its receptor -> opening bind with its receptors -> opening of ligand
of ligand gated Na+ (or Ca++) channels gated K+ or Clchannels or closure of Na+(or
• Influx of +ve ions makes the inside of Ca++) channels.
the cell membrane less negative ->> • Influx of -ve ions or efflux of +ve ions makes
lonic basis nearer to the firing level→ more the inside of the cell membrane more
excitable. negative -> away from the firing level ->
• During this potential the membrane is less excitable.
said to be facilitated i.e. needs a weaker • During this potential the membrane is said
stimulus to be excited than at rest. to be inhibited i.e. needs a stronger stimulus
to be excited than at rest.

A single EPSP have a mean amplitude of 1- A single IPSP have a mean amplitude of 1-5
Amplitude 5 mv, and reaches its peak value within 1-5 mv, and reaches its peak value within 1-5 msec
and Duration: msec, then gradually declines due to then gradually decays to nothing
current leakage.
EPSP is a local excitatory state. Up to 40-50 IPSP is a local response that can be summated
EPSPs have to be summated to reach by temporal or spatial summation in order to
threshold value needed to elicit an action inhibit an action potential from occurring.
potential.

3. Grand Post-Synaptic Potential:

Summation of IPSPs & EPSPs: A typical neuronal cell body receives thousands of presynaptic inputs
carrying sensory information from external and internal environment or from control centers in the
brain. At any given time, many presynaptic neurons may be firing at the same time and thus
influencing the postsynaptic neuron's level of activity.
Grand postsynaptic potential (GPSP) is the sum of all EPSPs and IPSPS occurring at approximately
the same time.

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 Physiology - CNS

Types of Summation:
1- Temporal (Time) summation: Summation of PSPs originating from ONE presynaptic neuron
stimulated by rapid repetitive stimuli.
2- Spatial (Space) summation: Summation of PSPs originating from MANY presynaptic neurons
stimulated simultaneously.

possible outcomes of the GPSP

1. If EPSP equals 2. If EPSP is slightly 3. If EPSP is much 4. If IPSP is more

IPSP more than IPSP more than IPSP than EPSP
→ the postsynaptic → the postsynaptic → the postsynaptic → the postsynaptic
membrane potential neuron don't reach neuron will reach neuron will be away
will remain close to threshold and the threshold and have from threshold and
resting level. membrane is said to an action potential. the membrane is said
be facilitated or in an to be inhibited or in
excitatory state. an inhibitory state.

Example:
Micturition reflex is influenced by many excitatory and inhibitory signals at one time, but the
response will vary according to the circumstances:
a- Sensory signals from receptors in the wall of the urinary bladder.
b- Facilitatory and Inhibitory signals from micturition center in the brain stem. c-
Voluntary control from the cerebral cortex.

Initiation of Action Potentials at the Axon Hillock:

➤ Axon hillock has lowest threshold in the whole neuron due to abundant voltage gated Na+
Channels.
➤ EPSPs occurring anywhere on the cell body or dendrites will be summated and spread
electrotonically (by current sink) throughout the whole neuron.
➤ Upon reaching the axon hillock, and due to presence of many low threshold voltage-gated Na
channels, it will be depolarized to the firing level thus initiating an action potential.

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 Physiology - CNS

B) Presynaptic Potentials:

Aspect Presynaptic Facilitation Presynaptic Inhibition

Neuronal Facilitatory neuron synapses with the Inhibitory neuron

local transient synapses
state with the axon
of hyperpolarization
Interaction axon terminal of a sensory neuron (axo- terminal of an excitatory
of postsynaptic membrane. neuron (axo-
axonic synapse). axonic synapse).
Neurotransmitter Facilitatory neurotransmitter (e.g., Inhibitory neurotransmitter (e.g., GABA).
Released serotonin).

Ion Channels Phosphorylates K+ channels, leading to Opens Cl channels or K+ channels.

Affected their closure.
Effect on
Prolonged depolarization of the presynaptic Hyperpolarization of the presynaptic
Presynaptic
Membrane membrane. membrane.

Impact on Ca2+ Increased Ca2+ influx due to prolonged Reduced Ca2+ influx due to decreased
Channels membrane depolarization. membrane depolarization.

Neurotransmitter Increased neurotransmitter release from Decreased neurotransmitter release from the
Release the presynaptic neuron. presynaptic neuron.

Impact on Synaptic Enhanced effectiveness of synaptic Reduced effectiveness of synaptic

Transmission transmission, prolonging the response. transmission to the postsynaptic neuron.

Functional Example
Sensitization, where sensory responses are Pain modulation, such as inhibition of pain
heightened. signals.

Enhances and prolongs neurotransmitter Allows selective modulation of synaptic

Significance release, affecting sensory processing. connections without affecting overall neuron
excitability.

Properties of Synaptic Transmission

1. Forward Direction:
Impulses are conducted at the synapse in only one way, from the presynaptic neuron to the
postsynaptic neuron. This is because neurotransmitters are formed and released from the
presynaptic neuron, not the postsynaptic one.
2. Synaptic Delay:
The time taken by an impulse to be conducted through the synapse, which lasts about 0.5
milliseconds.

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 Physiology - CNS

3. Fatigue:
Definition: A decreased rate of impulses discharged from the postsynaptic neuron after
repetitive stimulation of the presynaptic neuron.
Causes:
1. Exhaustion of synaptic vesicles in the presynaptic terminals.
2. Inactivation of postsynaptic receptors.
Significance: Synaptic fatigue stabilizes the nervous system, such as by stopping discharge
from overexcited areas in the CNS during epileptic seizures.
4. Effect of Changes in Composition of Internal Environment:
PH of the Blood:
Alkalosis: Increases the excitability of neurons and facilitates synaptic transmission due
to a decrease in ionized Ca2+, which may lead to convulsions (e.g., if an epileptic patient
hyperventilates, this may precipitate a fit).
Acidosis: Decreases synaptic transmission due to an increase in ionized Ca2+, which may
lead to coma (e.g., in diabetic ketoacidosis).
Hypoxia:
Inhibits synaptic transmission. Temporary interruption of cerebral circulation for 3-5
seconds may cause unconsciousness, and prolonged ischemia for minutes can cause
brain damage.
Hypoglycemia:
Glucose is the main fuel of the brain, so hypoglycemia inhibits synaptic transmission.
Hypocalcemia:
Decreased ionized Ca2+ in the extracellular fluid facilitates synaptic transmission as it
increases the excitability of the postsynaptic membrane, leading to tetanic convulsions.
5. Effect of Drugs:
Stimulants:
Theophylline, theobromine, and caffeine facilitate synaptic transmission by depolarizing
the postsynaptic membrane.
Depressants:
Analgesics, hypnotics, and anesthetics decrease synaptic transmission by
hyperpolarizing the postsynaptic membrane or by interfering with the synthesis, release,
or reuptake of certain neurotransmitters by presynaptic knobs.

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 Physiology - CNS

Toxins:
Strychnine: Competes with the inhibitory neurotransmitter at postsynaptic receptor
sites, blocking postsynaptic inhibition, which leaves excitatory pathways unaffected,
leading to convulsions, muscle spasm, and death.
6. Effect of Diseases:
Tetanus Toxin: Prevents the release of inhibitory GABA (or glycine) in the CNS,
causing spastic paralysis. This spasm occurs especially in jaw muscles (lockjaw) and then
affects respiratory muscles, leading to death.

Botulism Toxin: Blocks the release of excitatory acetylcholine at the neuromuscular

junction, leading to flaccid paralysis, which may cause respiratory muscle paralysis and
death.
Summary

Property Key points:

Forward
Impulses only move presynaptic to postsynaptic.
Direction
Synaptic Delay Transmission delay of ~0.5 ms.

Fatigue Reduced transmission with repetitive stimulation; stabilizes the nervous system.
pH Effect Alkalosis: Increases excitability. Acidosis: Reduces transmission.
Hypoxia Inhibits transmission; may cause unconsciousness.
Hypoglycemia. Reduces transmission due to lack of glucose.

Hypocalcemia Increases excitability, risk of convulsions.

Drug Effects Stimulants enhance transmission; depressants and toxins can inhibit or cause convulsions.

Tetanus: Causes spastic paralysis by blocking inhibitory neurotransmitters.

Diseases
Botulism: Causes flaccid paralysis by blocking excitatory neurotransmitters.

Synaptic Plasticity
Definition: The brain's ability to strengthen or weaken neuronal connections based on experience.
Mainly occurs in the hippocampus, important for learning and memory.
Memory Types:
• Short-Term: Lasts seconds to minutes.
• Intermediate-Term: Lasts up to 3 weeks.
• Long-Term: Can last a lifetime.

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 Physiology - CNS

Molecular mechanisms of Synaptic Plasticity:

1. Short term 2. Intermediate term

Post tetanic potentiation (PTP) Habituation Sensitization
Transient response of Gradual loss of response of Augmented
Separatesresponse
pre- andof
postsynaptic neuron postsynaptic neuron to postsynaptic
postsynaptic neuronallows
neurons; to
(enhancement of synaptic repeated benign stimuli (habituated) stimuli
diffusion of after
transmission) after (harmless) (insignificant). beingneurotransmitters.
coupled with noxious
Definition
application of brief tetanizing At first, evokes a reaction, one
train of stimuli after being repeated, evokes
less behavioral response
then Person ignores it

Duration Few seconds to minutes. May last up to 3 weeks.

Accumulation (build up) of Gradual inactivation of Ca2+ Separates facilitation

Presynaptic pre- and
Ca2+ in presynaptic neuron channels in Presynaptic postsynaptic
noxious stimulus neurons;
activates a
lonic basis
continuous release of terminal → Ca→ release of 3rd neuron
allows secreting
diffusion of
→

neurotransmitter until neurotransmitter serotonin

neurotransmitters.
Ca2+ pump remove it

Basic mechanism of Neglecting unimportant Separates

Walk pre-
through the and
woods.
immediate memory for a few stimuli e.g. getting used to At postsynaptic neurons;
first you are alert to noises
Example
facts, words, telephone noises then you habituate.
allows diffusionThen
of a
numbers (7-10) squirrel jumps on you
neurotransmitters.
You immediately become alert
and hyper responsive to any
voice or movement.

Filtering sensory information Defensive response; to avoid

Importance (irrelevant stimuli ) Focusing injury or discomfort
on important stimuli

Dr. Elsherif 11
 Physiology - CNS

2. long term
Long term potentiation (LTP): Long term depression (LTD)

Persistent increase in (post) synaptic Separates pre-

Persistent and postsynaptic
decrease neurons;
in (post) synaptic
Definition (response) strength after strong intensity allows diffusion
response after of neurotransmitters.
weak intensity low
high frequency stimulation. frequency stimulation

Duration last from days, weeks, years up to life time.

Requires permanent structural changes in the synapse, i.e. Protein synthesis →
Growth of presynaptic and/ or postsynaptic neurons and their connections

Stimulation of presynaptic neuron→ release Glutamate bind AMPA and NMDA receptors in
postsynaptic membrane.
Activation of AMPA receptors →Na inflow depolarizes PSM →relieves Mg block in NMDA
receptor channel, →Ca" inflow.

Ionic basis ➤ High frequency stimuli →rapid in Ca activates Calmodulin Kinase II →moves more
AMPA receptors into PSM→ ↑ synaptic response →↑ synaptic response LTP
➤ Low frequency stimuli →→slow ↑ in cytoplasmic Ca" →activates different cascade
(involving Calcineurin phosphatase 1)→ removal of AMPA receptors →↓ synaptic
response → LTD

contributes to long term memory storage Separates pre-

contributes and postsynaptic
to long term memoryneurons;
decay
Importance
(learning) allows diffusion of neurotransmitters.

Summary

1. Short term Intermediate-term Long-term (LTP & LTD)

(Habituation & Sensitization)

Habituation: Reduced response to Separates pre- and postsynaptic neurons;

Temporary enhancement of LTP: Increase in synaptic strength.
allows diffusion of neurotransmitters.
Definition synaptic transmission after harmless stimulus. LTD: Decrease in synaptic
Sensitization: Increased response strength.
brief stimuli
after harmful stimulus
Ca2+ buildup in presynaptic Habituation: Inactivation of Ca2+ LTP: High Ca2+ influx adds AMPA
channels. receptors.
lonic Basis neuron
Sensitization: Prolonged depolarization LTD: Low Ca2+ removes AMPA
from K+ channel closure receptors.

Duration Seconds to minutes Lasts up to 3 weeks Lasts days to lifetime

Remembering a phone number Habituation: Ignoring background LTP: Memory formation.

Example noise. LTD: Memory decay

Sensitization: Startling event

Temporary EPSP enhancement Habituation: Sensory filtering. LTP: Learning and memory.
Importance
Sensitization: Defense mechanism LTD: Weakening synapses.

Dr. Elsherif 12
 Physiology - CNS

Test yourself

1- The central nervous system is connected with the peripheral NS by all the following types of
nerve fibers, except:
a- postganglionic autonomic fibers b- preganglionic autonomic fibers
c- somatic motor fibers d- autonomic sensory fibers
2- Regarding inhibitory synaptic transmission mechanism, all statements are correct EXCEPT:
a. are always postsynaptic. b. may depolarize the presynaptic membrane.
c. may involve a postsynaptic increase in Cl- conductance.
d. tends to decrease the frequency of action potentials in the post synaptic nerve.
3- Regarding presynaptic inhibition:
a. the postsynaptic neurone membrane is hyperpolarized.
b. there is a decrease in the release of chemical transmitters from the presynaptic neuron
c. there is increased Ca2+ influx into the presynaptic neurone.
d. there is closure of K+ channels of the presynaptic neurone.
4- The release of neurotransmitter at a chemical synapse in the central nervous system is
dependent upon which of the following?
a- synthesis of acetylcholinesterase
b- hyperpolarization of the synaptic terminal
c- opening of ligand-gated ion calcium channels
d- influx of calcium into the presynaptic terminal
5- The excitatory or inhibitory action of a neurotransmitter is determined by which of the
following?
a- function of its postsynaptic receptor b-molecular composition
c- shape of the synaptic vesicle in which it is contained
d- distance between the pre- and post-synaptic membranes
6- Regarding synapses:
a- presynaptic knobs contain vesicles which have t-snare in their membranes
b- v-snare of the vesicles has high affinity to t-snare in the active zone of the presynaptic membrane.
c- Ca2+ voltage gated channels of the pre-synaptic knob open during repolarization
d- synaptic cleft contain high concentration of K+.

Dr. Elsherif 13
 Physiology - CNS

7- Excitatory postsynaptic potential:

a- cannot be summated. b- is a state of local depolarization.
c- is due to opening of voltage gated Na+ channels.
d- is due to opening of chemical gated K+ channels
8- Grand post-synaptic potential, may cause the postsynaptic membrane to:
a- be more excitable if EPSP > IPSP. b- be less excitable if IPSP > EPSP.
c- reach firing if there is summation of EPSPs d- all of the above
9- Presynaptic inhibition is characterized by:
a- decreased Ci- influx into presynaptic terminals
b- hyperpolarization of presynaptic terminals
c- increased Ca2+ influx into post-synaptic neuron
d- a 3rd neuron secreting serotonin
10- Synaptic transmission is terminated by which of the following?
a- block of postsynaptic receptors
b- elevation of Ca++ in presynaptic knobs
c- reuptake of neurotransmitters by postsynaptic neurons
d- degradation of neurotransmitters by specific enzymes
11- Regarding synapses:
a- synaptic cleft contain high K+ concentration
b- Ca++ voltage gated channels of the presynaptic knobs open during repolarization
c- extracellular Ca++ concentration equals that of intracellular
d- presynaptic knobs contain vesicles with V-Snare proteins in their membranes
12- Excitatory postsynaptic potential:.
a- shows reversal of polarity b- obeys all or none rule
c- cannot be propagated d- cannot be summated
13- The excitatory postsynaptic potential (EPSP) is:
a- produced as a result of release of GABA
b- a state of partial depolarization
c- due to increased permeability to Cl- in the postsynaptic membrane
d- unable to undergo summation

Dr. Elsherif 14
 Physiology - CNS

14- lonotropic receptors:

a- act by changing levels of intracellular CAMP b- are ligand gated ion channels
c- act by increasing intracellular IP3 d- are voltage gated ion channels
15- The inhibitory postsynaptic potential (IPSP) is:
a- produced as a result of release of acetyl choline
b- involved in the gate theory of pain control
c- a state of hyperpolarization
d- due to increased Na+ permeability in the postsynaptic membrane
16-IPSP differs from EPSP in:
a- being of short duration b- being unable to summate
c- moving the postsynaptic membrane potential away from threshold
d- being propagated at same rate as action potential
17- Presynaptic inhibition:
a- produced as a result of release of GABA b- leads to decreased release of neurotransmitter
c- is involved in the gate theory of pain control d- all of the above
18- Excitatory presynaptic potential:
a- needs excitatory 3rd neuron b- needs inhibitory 3rd neuron
c- leads to hyperpolarization of presynaptic membrane
d- directly excites the postsynaptic membrane
19- Temporal summation:
a- occurs by rapid repetitive stimuli originating from one presynaptic neuron
b- occurs by rapid repetitive stimuli originating from many presynaptic neurons
c- occurs by multiple stimuli originating from one presynaptic neuron
d- occurs by multiple stimuli originating from many presynaptic neurons
20- Synaptic transmission is stimulated by:
a- hypercalcemia b- alkalosis
c- acidosis d- botulism
21- Synaptic depression may result from all of the following EXCEPT:
a. botulin. b. hypoxia
c. acidosis. d. strychnine

Dr. Elsherif 15
 Physiology - CNS

22- Tetanus toxin leads to:

a- spastic paralysis due to inhibition of acetyl choline release
b- convulsions due to competitive inhibition with inhibitory transmitters
c- flaccid paralysis due to inhibition of GABA release
d- spastic paralysis due to inhibition of GABA release
23- Habituation of synapses:
a- is due to decrease release of neurotransmitters from the presynaptic neuron.
b- is due to nocious stimuli.
c- is due to increase Ca2+ influx in presynaptic neuron
d- a & c are correct
24- Post-tetanic potentiation is due to:
a- rapid active Ca2+ pump out of the presynaptic neuron.
b- repetitive stimulation of the presynaptic neuron not to the extent to produce fatigue
c- is due to nocious stimuli. d- repetitive benign stimuli at intervals.
25- Habituation is:
a- persistent decrease in synaptic strength after weak intensity stimuli
b- continuous discharge from postsynaptic neuron after brief tetanizing stimuli
c- gradual loss of response to repeated benign neutral stimuli
d- augmented response to repeated benign neutral stimuli
26- Habituation of synapses:
a. is due to excess release of neurotransmitters from the presynaptic neuron.
b. is due to noxious stimuli.
c. is due to increase Ca2+ influx in presynaptic neurone.
d. is due to a gradual decrease of response of the postsynaptic membrane due to inactivation of
calcium channels in presynaptic neurons.
27- Sensitization of synapses:
a- is due to decreased release of neurotransmitter from presynaptic neuron
b- causes hyperpolarization of postsynaptic neuron
c- is explained by presynaptic facilitation
d- is due to accumulation of Ca++ in presynaptic knob
Answers
1. A 6. B 11. D 16. C 21. D 26. D
2. C 7. B 12. C 17. D 22. D 27. C
3. B 8. D 13. B 18. A 23. A
4. D 9. B 14. B 19. A 24. B
5. A 10. D 15. C 20. B 25. C

Dr. Elsherif 16
 Physiology - CNS

Chemical Transmitters
(Neuro-Transmitters)

Chemical transmitter:
a substance that mediates chemical signaling between neurons.
Neurotransmitters:
are endogenous chemical substances released from presynaptic neurons that transmit
signals between neurons across a synapse.

A substance can act as a neurotransmitter in one region of the brain while serving as a
hormone elsewhere.

Types of neurotransmitters
More than 100 different chemical substances function as synaptic transmitters. In general, there are two
different groups of synaptic transmitters:

Small Molecule, Large

local transient stateMolecule,
of hyperpolarization

Rapidly Acting Transmitters of postsynaptic membrane.

Slowly Acting Neuropeptides
Synthesis & Synthesized in presynaptic cytosol; stored in Synthesized in soma; transported to terminal
Storage small vesicles knobs in large granular vesicles

Recycling Vesicles continually recycled and reused Vesicles autolyzed and not reused
Release Rapid, in large amounts Slower, in smaller amounts but more potent

Action Stimulate ionotropic receptors, leading to Stimulate metabotropic receptors, activating

rapid ion channel activation 2nd messenger systems

Response Acute responses (e.g., sensory signal Prolonged effects (e.g., long-term changes in
transmission, motor control) ion channels, receptors, genes)

• Acetylcholine Biogenic Amines: • Hypothalamic Releasing Peptides: TRH CRH

Epinephrine. Norepinephrine. Dopamine. Somatostatin
Serotonin. Histamine • Pituitary Peptides: GH. TSH ACTH
• Amino Acid Neurotransmitters: • Opioid Peptides: Endorphins. Enkephalins
Categories
Excitatory: Glutamate, Aspartate. • GIT Peptides: CCK. VIP. Gastrin. Substance P
Inhibitory: GABA, GlycineGases: Nitric • Other Peptides: Substance P. Angiotensin I.
Oxide (NO) Neuropeptide Y. ANP. BNP. Sleep Peptides
• Purines: Adenosine

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 Physiology - CNS

Some Neurotransmitters and their functions

Neurotransmitter Function Examples of Malfunctions

Enables muscle action, learning, and With Alzheimer's disease, ACh-producing
Acetylcholine (ACH)
memory. neurons deteriorate.

Dopamine Influences movement, learning, Oversupply linked to schizophrenia.

attention, and emotion. Undersupply linked to tremors and decreased
mobility in Parkinson's disease.

Affects mood, hunger, sleep, and Undersupply linked to depression. Some

Serotonin
arousal. antidepressant drugs raise serotonin levels.

Norepinephrine Helps control alertness Undersupply can depress mood.

and arousal.

GABA (gamma- Undersupply linked to seizures, tremors,

A major inhibitory neurotransmitter.
aminobutyric acid) and insomnia.

A major excitatory neurotransmitter; Oversupply can overstimulate the brain,

Glutamate involved in memory. producing migraines or seizures (which is why

some people avoid MSG, monosodium
glutamate, in food).

Dr. Elsherif 18
 Physiology - CNS

Neuronal Pools

Definition: A neuronal pool is a collection of neurons carrying the same function ni CNS e.g. cortical
neuronal pool, cerebellar neuronal pool and so on.
- The CNS is composed of thousands to millions of neuronal pools.
- Although each neuronal pool has its own arrangement of neuronal circuits, they al share certain
similarities of organization.

Similar Organizations

(1) Divergence (2) Convergence

Definition One neuron stimulates many neurons many neurons stimulate one neuron

Divergence in same direction Convergence excitatory & inhibitory signals

→ Amplification: e.g. one cortical cell from different sources → allows summation
stimulates many AHCs & many and integration of information from different
Function
muscle fibers sources:
Divergence in different directions a) motor neuron receives signals from a)
→ Distribution: e.g. painful stimulus peripheral sensory fibers,
Stimulate AHCs of muscles on b) propriospinal fibers,
same & Opposite side & Ascends c) corticospinal tract from the motor cortex.

to brain stem, sensory cortex. →to control muscle function

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(3) Excitation field:

Definition: It is the number of neurons, with which one afferent neuron synapses.

a) The Discharge (excited) zone:

- Neurons that lie in the center of the field receive large numbers of knobs. When the afferent

nerve is stimulated, these cells are stimulated enough to reach to the threshold value and

discharge nerve impulses.

b) The Facilitated zone (subliminal or subthreshold zone).

- Neurons that lie in the periphery of the field receive few numbers of knobs. So they are only

facilitated when the afferent is stimulated.

- The area of discharge zone and subliminal fringe depends on the strength of the stimulus: the

stronger the stimulus the wider the discharge zone

- This arrangement leads to phenomenon of Facilitation

Definition: If the excitation fields of two input neurons overlap at the peripheral facilitation

zones (subliminal fringe), the outcome of the two pools when stimulated simultaneously is

more than the sum of outcome of both pools, when each neuron is stimulated separately

Function: the two neighboring neurons facilitate each other > Example: Referred pain

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(4) Inhibitory circuits:

prevent excessive signals→ stabilize nervous system

a. Lateral inhibition: stimulation of one excitatory neuron→ cause
• Stimulation of Central neuron
• Inhibition of Peripheral neurons via inhibitory interneuron
Functions: sharpen the sensation
Examples:
1.Skin: tactile localization
2.Retina: horizontal cells inhibit peripheral
bipolar cells to prevent blurring &
sharpen the vision.

b. Reciprocal innervation: stimulation of one excitatory neuron

• Stimulation of muscle
• Inhibition of antagonist via inhibitory interneuron
Function: Enables muscle to contract freely (unopposed)
Example:
Flexor withdrawal reflex: painful stimulus stimulates flexors and inhibits extensors

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c. Negative feedback inhibition:

• Stimulated motor neuron → gives off recurrent collateral →synapse with inhibitory
Interneuron (Renshaw cell) →terminates on motor neuron itself & surrounding neurons
Functions: Focusing and sharpening of the effect.
Example:
1. Dampens activity of motor neurons
2. Prevents over excitation

(5) Activating circuits "after discharge":

Definition: output neuron continues to discharge after stoppage of input neuron

b. Reverberating /oscillatory
a. Parallel circuits:
close circuits
Input connected to output by parallel Output neuron sends collateral to re-excite the
circuits (different number of input of the same circuit
Definition
interneurons → their signals (Positive feedback)
converge onto one output neuron.

prolongation of discharge after input the most important circuits → discharge for a
Function
signal is over. long period or even the whole life

When looking at an image, you will base of wakefulness / sleep / other tonically
Example
not notice when you blink. discharging centers, e.g. R.C.

determined by:
a-Number of synapses
Duration b- Fatigue of the synapses.
c- Facilitatory or inhibitory impulses
entering the circuit.

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Summary

Concept Definition Function/Example

One neuron stimulates many a) Amplification of signal (e.g., motor neuron →
Divergence neurons. many muscle fibers). b) Distribution of signal
(e.g., pain stimulus → brain)

Summation and integration of signals (e.g.,

Convergence Many inputs stimulate one neuron. motor neuron receives sensory and motor
cortex inputs).

Number of neurons synapsed by one a) Discharge zone: neurons fire. b) Facilitated

Excitation Field afferent neuron. zone: neurons are partially activated. Example:
Referred pain.

Lateral Central neuron is stimulated; Sharpens sensation (e.g., tactile localization,

peripheral neurons inhibited. vision).
inhibitory circuit

Inhibition

Negative Neuron inhibits itself via Prevents over-excitation (e.g., dampens motor

Feedback interneuron. activity).

Reciprocal One muscle stimulated, antagonist Enables smooth movement (e.g., flexor reflex).
Innervation inhibited.
activating circuits

Parallel After- Input neuron stimulates several Prolongs signal (e.g., unnoticed blinking).
Discharge chains converging to one output.

Reverberat Positive feedback loop within Keeps signals active (e.g., essential for
ory Circuits circuit. wakefulness, breathing).

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Test yourself
1 - Divergence:
a- helps amplification of the signal.
b- means that several input fibres supply a single neuron.
c- helps the process of summation. d- explains the process of occlusion
2 - Regarding the excitation field:
a- neurons in the periphery receive large number of knobs.
b- are of the discharge zone is in the periphery.
c- neurons in the centre receive large number of knobs.
d- neurons in the periphery are inhibited
3 - Renshaw cell:
a- is activated by glycine.
b- shows the phenomenon of negative feedback inhibition.
c- is present in dorsal horn of the spinal cord. d- are excitatory neurons.
4 - Occlusion:
a- occurs due to overlap of facilitation zones of two adjacent neuronal pools
b- occurs due to overlap of discharge zones of two adjacent neuronal pools
c- increases the combined effect of two adjacent neurons when stimulated simultaneously
d- is continued output discharge after stoppage of stimulation of input
5 - Lateral inhibition:
a- helps sharpening of sensation b- needs only inhibitory neurons
c- occurs by inhibition of a central neuron and exciting the surrounding neurons
d- occurs by one type of chemical transmitter
6 - Neuropeptides:
a- are synthesized in the presynaptic knobs
b- are synthesized sized in the soma of the neuron
c- consist of small molecules d- are rapidly acting
7 - All the following transmitters are neuropeptides except:
a- neuropeptide b- somatostatin
c- dopamine d- enkephalin

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8 - Receptor potential:
a- is actively conducted to the 1st node of Ranvier.
b- has a duration shorter than that of the action potential.
c- amplitude is proportional to the intensity of the stimulus.
d- is due to specific increase of the membrane permeability to Na+ ions
9 - Tonic receptors include all of the following, EXCEPT:
a- touch receptors. b- nociceptors.
c- baroreceptors. d- muscle spindles.
10 - As regards the Properties of the receptor potential:
a- it is actively conducted to the 1st node of Ranvier.
b- its duration is 0.5 msec.
c- it is accompanied by absolute refractory period
d- it does not obey the all or non rule.
11 - Receptor potential initiated by an adequate stimulus:
a- develops always at it full magnitudes
b- undergoes temporal summation only
c- undergoes spatial summation only
d- could initiate an action potential

Answers
1. A 5. A 9. A
2. C 6. B 10. D
3. B 7. C 11. D
4. B 8. C

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