PHYSIOLOGYPHYSIOLOGY

THE SYNAPSETHE SYNAPSE

Dr. Ramadan Mohamed Ahmed

What is a synapse?

A synapse is the junction between 2 neurones.

Histological Types of synapse1. Axodendritic axon & dendrite.

2. Axosomatic axon & soma.

3. Axoaxonal axon & axon.

Type of Synapse

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SYNAPSES (cont.)SYNAPSES (cont.)Types of Synapses:

1. Electrical Synapses: v. rare in human NS, common in cardiac & smooth ms. - Can act in either direction.

2. Chemical Synapses: common in human NS- Impulses can only travel in one direction (= one-way

conduction).

electrical synapse

Gap Junction

Protein channel

Chemical synapse

SYNAPSES SYNAPSES Funtional Anatomy of Chemical Synapses:► Presynaptic Neuron:- Presynaptic knob cpntains synaptic vesicles that store NT.- At its end there is the active zone which has docking sites for vesicles. - Both, vesicles & active zone, contain proteins called SNARE proteins.

► Synaptic Cleft:It is a 20-30 nm E.C. space, whichseparates pre- & postynaptic neurons.

► Postsynaptic Neuron:- The membrane opposite presynaptic knob is called postsynaptic density.- It has a large number of receptors that are specific for the NT that is released from the adjacent presynaptic knob.

SYNAPSES SYNAPSES Types of Receptors in Postsynaptic Neuron:1. Ionotropic Receptors: Formed of: a) a binding protein that unites with the NT b) a ligand-gated ion channel, which may be a Na+, K+ or Cl- channel.

2. Metabotropic Receptors: Are receptors linked to G-proteins. They activate a 2nd messenger, which has one of the following effects on postsynaptic neuron:

a) opens ion channels b) influences metabolic

activities c) binds to the nucleus

& influences synthesis of new proteins (e.g., receptors or channels).

Mechanism of Synaptic TransmissionMechanism of Synaptic Transmission

Mechanism of Synaptic TransmissionMechanism of Synaptic Transmission1. Action potential arrives at presynaptic knob. 2. Opening of voltage-gated Ca2+ channels by depolarization influx of Ca2+ according to concentration gradient. N.B.: I.C. [Ca2+] is kept low by a Ca2+ pump which extrudes Ca2+.3. Movement of vesicles toward their docking sites in the active zone when Ca2+ binds to their membrane. 4. Fusion of vesicles to active zone by formation of complexes between the SNARE proteins on the vesicles & those on presynaptic membrane. 5. Release of NT by exocytosis into synaptic cleft.6. Diffusion of NT across synaptic cleft.7. Binding of NT to its receptor in postsynaptic membrane.8. Opening of ligand-gated ion channels.9. Removal of NT from synaptic cleft terminates action of NT by: a. active reuptake b. enzymatic destruction

c. passive diffusion d. removal by glial cells.

Mechanism of Synaptic Mechanism of Synaptic transmissiontransmission

Acetylcholinereceptor site

action potential reachesaction potential reachesaxon terminal axon terminal

DiffusionDiffusion of Caof Ca++++ into the into theterminal button terminal button

causescausesrelease of ACh fromrelease of ACh from

vesicles into thevesicles into the cleft by exocytosiscleft by exocytosis

Synaptic cleft

Chemically gatedcation channel

Motor end plate

POSTSYNAPTIC POTENTIALSPOSTSYNAPTIC POTENTIALS1. Excitatory Postsynaptic Potential (EPSP) If an excitatory NT (e.g., ACh) binds to its specific receptors, a state of

partial depolarization of postsynaptic membrane (= graded potential) will occur, as it causes opening of Na+ channels.

Na+ enters according to conc. & electric gradients inside becomes less negative than at rest, i.e., closer to the firing level.

Na+ influx is proportional to the amount of NT released by presynaptic knob. Membrane is said to be “facilitated”, i.e., it requires a weaker stimulus to be

excited than at rest.

POSTSYNAPTIC POTENTIALS (cont.)POSTSYNAPTIC POTENTIALS (cont.)2. Inhibitory Postsynaptic Potential (IPSP) If an inhibitory NT (e.g., GABA) binds to its specific receptors, a state of

hyperpolarization of postsynaptic membrane will occur, as it causes opening of Cl- (mainly) or K+ channels.

Cl- enters (or K+ leaves) according to conc. gradient inside becomes more negative than at rest, i.e., away from firing level.

Cl- influx (or K+ efflux) is proportional to the amount of NT released by presynaptic knob.

Membrane is said to be “inhibited”, i.e., it requires a stronger stimulus to be excited than at rest.

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8 EPSP influx Na+, Ca2+ & prevent efflux K+

9. EPSP AP

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Cl-

K+

8 IPSP Influx of Cl- (GABA) &

efflux K+

(Dopamine). 89

9. IPSP not generate AP

Excitatory Synapse (EPSP) & Inhibitory synapse (IPSP)

Excitatory synapse (EPSP)

Serotonin (5HT), ACh, Glutamate

Inhibitory synapse (IPSP)

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Inhibitory synapse

Excitatory synapse

Inhibitory Synapse (IPSP)

IPSP Influx Cl-

(GABA) & efflux K+

(Dopamine).

EPSP influx Na+,

Ca2+ & decrease K+ efflux

EPSP reach threshold AP

IPSP do not generate AP

Hyper polarization of post synaptic

membrane potential inhibition

Depolarization of post synaptic membrane potential excitation

NT: Serotonin

(5-HT), ACh, Glutamate, NE.

Excitatory synapse (EPSP)

A single EPSP cannot induce an action potentialEPSPs must summate temporally or spatially to

induce an action potentialTemporal summation – presynaptic neurons

transmit impulses in rapid-fire orderSpatial summation – postsynaptic neuron is

stimulated by a large number of terminals at the same time

IPSPs can also summate.

Summation

Summation

Characteristics of EPSP & IPSP

1. Local event & do not spread

2. No threshold and can be summed:

I. temporal summation on same nerve when stimulate few times.

ii. Spatial summation on different nerve

3. Do not follow all or none event and can be graded (size of amplitude depend on strength of stimulant)

4. Ca2+ is need to release NT

5. Single EPSP can not dep. Post-neuron to achieve threshold to generate A.P.

6. Single IPSP can not hyperpolarisation on Post-neuron to inhibit A.P.

Initiation of AP at Axon Hillock:The firing level (=threshold potential) is not the same

throughout the postsynaptic neuron.

The lowest threshold is present at the axon hillock, because this region has an abundance of voltage-gated Na+ channels, making it more sensitive to change in potential than the rest of the cell body & dendrites.

EPSPs occurring anywhere in dendrites or cell body spread by passive local current flow (see lecture 3) and may depolarize the axon hillock to firing level, initiating an AP that spreads along axon & results in release of NT by postsynaptic neuron.

Synaptic inhibition(1) Inhibitory post synaptic potential (EPSP)

(2) Presynaptic Inhibition

Synaptic inhibition[3] Negative feedback inhibition: (Recurrent

inhibition)

Characteristics of synaptic transmission

1. One-way pre-neuron to post neuron.

2. Synaptic delay time need to release NT& allow NT bind at post-synapse to caused response.

3. Synaptic fatigue failure of post-synapse in response to high rate of impulses (epilepsy stop due to exhausted of NT.

4. Post tetanic facilitation postsynaptic neuron can become more excitable when receive repetitive stimulation.

5. pH : acidosis decrease synaptic transmissionWhile alkalosis increase.

6. Hypoxia O2 supply to brain , so decrease synaptic transmission.

7. Summation of postsynaptic potentials either spatially or temporally.

8. Drug effect:1. Excitability of neuron increase close to threshold

caffeine, & theophylline. Also strychnine increase synaptic transmission.2. Hypnotic & anesthetic drugs threshold cause

synapse less excite, release & synthesis of NT.

9. Diseases:1. Tetanus toxin (= toxin produced by Clostridium tetani): inhibit release of inhibitory neurons ms.

contraction.2. Botulism toxin (toxin produced by Clostridium

botulinum): prevent release of acetylcholine.

10. Synaptic plasticity:It is the ability to change the function of synapse according to the demand i.e the synaptic transmission

can be increased or decreased for short or long duration by repeated stimulus.

A) Post-tetanic potentiation If the pre-synaptic neuron is stimulated by brief rapid (tetanizing) stimuli, the post synaptic neuron

response will continue for few seconds to minutes after stoppage of the stimulus.Mechanism Increased Ca++ in pre synaptic neuron continuous release of chemical transmitter.

B) Habituation It is the gradual loss of response to a benign stimulus, when it is repeated for several times at

intervals.Mechanism Decrease Ca++ in presynaptic neuron caused by unknown gradual Inactivation of Ca++ channels

decrease release of chemical transmitter.

C) Sensitization It is the prolonged augmented response due to application of a noxious stimulus accompanying the

benign stimulus.Mechanism

Presynaptic Facilitation The 3rd neuron is excitatory neuron; which secretes serotonin. Serotonin increase cAMP in the presynaptic terminals. cAMP Phosphorylates a protein in the K+ channels and close them.. This prevents repolarization

& prolongs depolarization. Depolarization Keeps Ca++ channels opened Increase release of the chemical transmitter.

Presynaptic facilitation

Neuronal PoolA collection of neurons having the same function.

(1) Convergence Many neurons activate one neuronIt allows for spatial summation.Interpretation of many information received by

one neuron.

(2) Divergence One neuron activates many neurons.a. Amplification e.g One cortical cell activates

1000 AHCs in sp.cd.b. Distribution of signals.

Neuronal Pool

(3) Excitation field, discharge zone & subliminal fringe

Excitation field = neurons excited

by one input afferent fibre.

Discharge zone = central neurons

in which the excitation is above the

threshold value so they discharge.

Facilitation zone (subliminal Fringe)

peripheral neurons in which the

excitation is below the threshold value.

Weak stimulus small excitation field formed mainly of subliminal Fringe.

Occlusion summation

Stimulation at A

Stimulation at B

Stimulation at A & BAP 9+9 = 18

Stimulation at A

Stimulation at B

Stimulation at A & B AP 3+3 =6 but actual 9

Subliminal Fringe Summation

Neuronal Pool

(4) Reciprocal Innervation in which a sensory signal stimulates the neurons

supplying group of muscles, meanwhile it inhibits their antagonists through

stimulation of inhibitory interneurones. This enables the contracting muscle to function freely e.g. flexor withdrawal reflex.

Neuronal Pool

(5) After dischargeThe output continues to discharge after stoppage of stimulation of

the input.Mechanism: [a] Prolonged action of the neurotransmitter on the postsynaptic

receptor till it becomes completely inactivated.[b] Parallel circuits: The input is connected to the output by many parallel circuits, each contains different numbers of interneurones and so different

numbers of synapses.[c] Reverbrating circuits: The output neuron sends collateral restimulate itself. It can be stopped by: Fatigue Inhibition from other areas.

Neuronal Pool

(6) FatigueDecrease rate of discharge in post synaptic neuron due

to rapid repetitive stimulation.Mainly due to exhaustion of chemical transmitter in

presynaptic terminal.

(7) RecruitmentRecruitment is the gradual increase to a maximum in a

reflex when a stimulus of unaltered intensity is prolonged.

There is progressive increase in the activity of the interneurons, leading to an increase in the excitability of more and more motor neurons, until spatial summation raises the excitability to the threshold value to discharge.

Neuronal Pool

(8) Central delay It is the time passed during impulse transmission in the

synapses included in the pathway of the reflex arc.

CalculationCentral delay = Total reflex time - time of transmission

in the afferent and efferent neurons.Total reflex time = It the time passed from stimulation

till appearance of response.

ImportanceEstimation of the number of synapses in the reflex arc

pathway = Central delay / 0.5 msec (single synaptic delay).