Synaptic Transmission 6p1w3w

Synaptic Transmission Synapse is the site of junction between two neurons. With no protoplasmic continuity.

Transmission at the synapses may be 1. Electrical By low resistance gap-channel pathway that allow age of ions from one cell to another. Not Sensitive to drugs. Rare in CNS. (CEREBELLUM AND VESTIBULAR SYSTEM). 2. Chemical By release of a chemical substance from presynaptic terminal to act on postsynaptic cell. Sensitive to drugs.

Types of synapses 1. Axo-dendritic: most numerous, least excitable. 2. Axo-somatic: 3. Axo-axonic: least numerous,

Most excitable (low threshold).

Because of the numerous Na channels in the axon hillock.

Functional anatomy (A) Synaptic knobs: contain 1. mitochondria. (ATP synthesis). 2. Vesicles containing; neurotransmitters. 3. Large number of Ca channeles & release sites for neurotransmitters. (b) Synaptic cleft: 30-50 nm width & contains extracellular fluid. (c) Synaptic gutter: Post synaptic membrane Contains receptors for neurotransmiiters, protein channels and enzymes for destruction of neurotransmitters.

Mechanism Of Synaptic Transmission (1) Release of the chemical transmitter Action potential in the presynaptic nerve opens voltage gated Ca++ channels. leading to rupture of vesicle and release of the chemical transmitter in the synaptic cleft by exocytosis. The amount of the transmitter release α amount of Ca++ in the presynaptic terminal.

(2) The chemical transmitter crosses the synaptic cleft (3) Union of chemical transmitter with its receptors This changes the permeability of the post synaptic membrane to one or more ions.

(4) Changes in ion Fluxes: lead to change in resting membrane potential: less negative causing excitatory post synaptic potential.(EPSP) by opening of Na channeles. More negative causing inhibitory postsynaptic potential.(IPSP) by opening of K or Cl channeles.

Electrical events at synapse Postsynaptic Potentials (a) Excitatory post synaptic potential (EPSP) - It is a state of partial depolarization. - Occurs after release of excitatory neurotransmitters by about 0.5 msec. - During this response, the excitability of the neuron to other stimuli is increased. - It is caused by opening of ligand gated Na+ channels and closure of the ligand gated K+ channels or CL channeles.

- To reach the threshold value, EPSPs must be summated: (1) Time (temporal) summation: One presynaptic Knob is stimulated repetitively. Each EPSP must occur in postsynaptic membrane before the ending of the previous one. N.B. In temporal summation, the time between stimuli must be less than the duration of the EPSP. (2) Space (spatial) summation: Several presynaptic knobs are stimulated simultaneously. When the excitation reaches the firing level, action potential starts. 50 EPSPs are needed to reach the firing level.

(B) Inhibitory post synaptic potential (IPSP) - It is a local state of hyperpolarization. - Occurs due to release of inhibitory neurotransmitters as glycine. - It begins after about 1 msec. - During this response, the excitability of the neuron to other stimuli is decreased. - It is caused by opening of ligand gated CL channels (leading to CL influx) & K + channels leading to K influx). - Both events making the postsynaptic membrane more negative (hyperpolarization) making it away from firing level.

Types Of Synaptic Inhibition (1) Inhibitory post synaptic potential (EPSP) - Directly by release of inhibitory neurotransmitter leading to hyperpolarization. - Indirectly during the refractory period of a previous stimulus.

(2) Presynaptic Inhibition - The axon terminals of inhibitory neuron end at the axon terminals of an excitatory neuron. (Axo-axonic synapse). - The 3rd neuron releases an inhibitory transmitter which Opens Cl- channels of the excitatory neuron which Closes the voltage gated Ca channels. - The end result is reduced Ca++ entry to the synaptic knob and, in turn, decrease release of the transmitter.

- e.g. presynaptic inhibition at Substantia gelatinosa of Rolandi during pain control.

Properties of Synaptic Transmission (1) Forward direction i.e from pre to postsynaptic neuron. (2) Synaptic delay

= 0.5 msc.

It is the time needed for release of neurotransmitter and binding of the transmitter to receptors until generation of postsynaptic response. The more the number of synapses, the slower the conduction.

(3) Fatigue Def: Decrease rate of discharge in post synaptic neuron due to repeated stimulation of presynaptic neuron. Mainly due to decrease amount of chemical transmitter which stored in presynaptic terminal. Importance It prevents over excitation in CNS. (It is a gift from the god to the epileptic patients).

(4) Synaptic potentiation

Def 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.

(5) Effect of acidosis and alkalosis [I] Alkalosis; increased excitability → increase transmission convulsion. [II] Acidosis; decreased excitability & transmission coma.

(6) Effect of Hypoxia Due to accumulation of acids, hypoxia leading to decrease transmission. Prolonged ischaemia causes brain damage.

(7) Affected by Drugs [I] Drugs which increase synaptic transmission.

- Theophylline and caffeine (decrease threshold for excitation). - Strychnine blocks the action of the inhibitory transmitters. [II] Drugs which decrease synaptic transmission. - Analgesics, hypnotics, anaesthetics (-- the amount of excitatory neurotransmitters or enhancing the inhibitory neurotransmitters).

(8) Synaptic plasticity: Short and long term changes in synaptic function on the basis of past experience.

Forms of Synaptic plasticity A) Post-tetanic potentiation Def If the pre-synaptic neuron is stimulated by brief rapid (tetanizing) stimuli, the post synaptic neuron response will be enhanced & continue for about 60 seconds after stoppage of the stimulus. Mechanism Increased Ca++ in pre synaptic neuron → continuous release of chemical transmitter.

B) Habituation Def

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 Def It is the prolonged augmented response due to application of a noxious stimulus accompanying the benign stimulus to which the animal has been habituated. 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++ achannels opened → Increase release of the chemical transmitter.

Neuronal Pool Def: A collection of neurons having the same function.

Neuronal Pool Organization (1) Convergence Many neurons activate one neuron It allows for spatial summation. Interpretation of many information received by one neuron. It can be from single source or from multiple sources.

(2) Divergence One neuron activates many neurons. Its functions are: a. Amplification of the response. b. Distribution (spread) of signals.

(3) Excitation field, discharge zone & subliminal fringe Excitation field = neurons excited by synaptic knobs of one input afferent fibre.

Discharge zone= central neurons in which the excitation is above the threshold value so they discharge. (this part receive large number of synaptic knobs). Facilitation zone (subliminal Fringe) = peripheral neurons in which the excitation is below the threshold value (this part receive few number of synaptic knobs). Weak stimulus → small excitation field formed mainly of subliminal Fringe.

This arrangement leads to the development of 2 other phenomena Occlusion

Facilitation

Simultaneous stimulation of two afferent fibres. - Close to each other - not close to each other - by maximal stimuli - by submaximal stimuli Results in reflex reaction which is less than the sum more than the sum of the separate stimulation of the two input fibres. Cause: Overlap of the Discharge zones Facilitation zones (subliminal fringe).

@ Occlusion: This means occurrence of a smaller response when 2 near afferent neurons are maximally stimulated simultaneously than the algebraic sum of the responses obtained each afferent.

@ Subliminal fringe summation

(Facilitation):

It is the occurrence of a greater response when 2 afferent neurons (that are not very close to each other) are sbumaximally stimulated simultaneously than the algebraic sum of the responses obtained when each afferent is stimulated separately.

(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.

(5) After discharge Definition The 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 i.e decreased chemical transmitter. - Inhibition from other areas.

(6) Recruitment - Recruitment 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.

Synaptic Transmitters Classified into 2 main groups: A) Rapidly acting, small molecule neurotransmitters : according to chemical structure 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:

Nitric oxide (NO).

Rapidly acting, small molecule neurotransmitters: generally responsible for acute responses as sensory and motor signals.

B) Slowly acting, large molecule neurotransmitters : e.g. hypothalamic releasing hormones Generally they responsible for prolonged actions as long term opening and closure of ion channels. Most of neurotansmitters produce localized effects when released into synaptic cleft, while others released directly into blood producing effects at some distance from their site of release. A neuron usually secretes one transmitter, but some neurons secrete 2 or 3 transmitters called co-transmitters.

Acetylcholine (ACh) Sources: - neurons in many areas of the brain, - motor neurons that innervate skeletal muscles, - preganglionic neurons of the ANS, - postganglionic neurons of the parasympathetic nervous system, - some of the postganglionic neurons of the sympathetic nervous system. Effects : ACh has an excitatory effect, though it has inhibitory effects at some peripheral parasympathetic nerve endings.

Norepinephrine (NE) Is secreted by many neurons located in the brain reach widespread areas of the brain. In most of these areas, NE probably activates excitatory receptors, but in few areas, it activates inhibitory receptors. NE is also secreted by most of the postganglionic neurons of the sympathetic neurons system.

Dopamine Is secreted by neurons that originate in the substantia nigra and which terminate mainly in the basal ganglia. The effect of dopamine is usually inhibition.

Serotonin Is secreted by neurons that originate in the median raphe of the brain stem, and project to many brain and spinal cord areas. Serotonin is inhibitory.

Gamma-aminobutyric acid (GABA)

Is secreted by nerve terminals in the spinal cord, cerebellum, basal ganglia and cortex. It causes inhibition.

Glycine Is secreted mainly at synapses in the spinal cord. It is an inhibitory transmitter.

Glutamate Is secreted by presynaptic terminals in many sensory pathways, and in many areas in the cortex. It causes excitation.

Nitric oxide (NO) Occurs especially in areas of the brain that are responsible for long-term behaviour and for memory. [It is synthesized instantly as needed, and diffuses into the immediately adjacent postsynaptic neuron as well as other postsynaptic neurons nearby]. It modifies neuronal excitability for seconds, minutes or even longer (by changing intracellular metabolic functions).