Synapse 2.ppt

SYNAPSE – PART 2  SYNAPTIC TRANSMISSION Process by which the information from presynaptic neuron passes to the post synaptic neuron through the synapse 1. Action potential[AP] reaches synaptic knob 2. Opening of voltage gated calcium channels 3. release of neurotransmitter [NT] from synaptic...

SYNAPSE – PART 2  SYNAPTIC TRANSMISSION Process by which the information from presynaptic neuron passes to the post synaptic neuron through the synapse 1. Action potential[AP] reaches synaptic knob 2. Opening of voltage gated calcium channels 3. release of neurotransmitter [NT] from synaptic vesicles 4. Development of EPSP & IPSP 5. removal of NT from synaptic cleft 6. development of AP  4.DEVELOPMENT OF POST SYNAPTIC POTENTIALS-EPSP & IPSP Binding of NT to post synaptic receptors  opening of channels through which ions can flow The membrane of the postsynaptic neuron contains large numbers of receptor proteins, It has two important components: 1.Binding component 2.Ionophore component (1) a binding component that protrudes outward from the membrane into the synaptic cleft here it binds the NTcoming from the presynaptic terminal (2) ionophore component passes all the way through the postsynaptic membrane to the interior of the postsynaptic neuron. The ionophore in turn is one of two types: A. an ion channel that allows passage of specified types of ions through the membrane or B. "second messenger" activator - protrudes into the cell cytoplasm and activates one or more substances inside the postsynaptic neuron. - These substances in turn serve as "second messengers" to increase or decrease specific cellular functions.  The following events take place in postsynaptic cell:  NT binds with Ligand gated ion channels Cation channels – NT[usually glutamate] + receptor [R] Na + influx ----- depolarization of post synaptic membrane -------excitation[EPSP] Anion channels – NT[usually glycine & GABA] + receptor[R] Cl- influx ----- hyperpolarization of post synaptic membrane -------inhibition[IPSP]  NT binds with Second messenger activator G protein linked receptor + NT prolonged post synaptic excitation / inhibition A cascade of biochemical reactions that :generates a second messenger leads to change in ionic permeability of the cell Second messenger activator  Thus, Depending upon the ion[cation/anion] and the direction of their movement, the membrane potential of the post synaptic membrane changes either towards depolarization or hyperpolarization This change in membrane potential called synaptic potential creates signal in the post synaptic neuron  EPSP-Excitatory post synaptic potential If the potential change in the synaptic transmission is towards depolarization, the potential is called EPSP The depolarizing response begins.5 ms after the afferent impulse , reaches a peak in 1 -1.5 ms, then decrease exponentially. During this potential the excitability of the neuron to other stimuli is increased, therefore called EPSP Most common excitatory NT in CNS is glutamate Ionic basis of EPSP - NT + R causes Opening of Na+ channels ↑ Na+ influx Opening of Ca+ +channels ↑ Ca+ + influx Closing of Cl- channels ↓ Cl - influx Closing of K+ channels ↓ K+ efflux All these make the post synaptic neuron depolarized / more positive / excited Thus, Net ↑ in cations inside post synaptic neuron -----local depolarization ------ EPSP EPSP and IPSP  Summation Spatial summation- when more than one synaptic knob is active at the same time , the activity of one knob facilitates the activity of the other knob EPSPs summate & reach firing level AP[Action potential] results Temporal summation-repeated activity of a synaptic knob in quick succession causing new EPSP before previous EPSP has decayed EPSPs summate & reach firing level AP results  IPSP- inhibitory post synaptic potential If the potential change in the synaptic transmission is towards hyperpolarization, the potential is called EPSP hyperpolarization of post synaptic neuron leads to inhibition of the postsynaptic neuron The hyperpolarizing response begins 1-1.5 ms after the afferent impulse , reaches a peak in 1.5-2 ms, then declines exponentially. During an IPSP the excitability of the neuron to other stimuli is decreased IPSP’s are produced by inhibitory NT’s GABA ,glycine Ionic basis of IPSP - NT + R causes Opening of Cl- channels ↑ Cl- influx Opening of K+ channels ↑ K+ efflux Closing of Na+ channels ↓ Na+ influx Closing of Ca+ + channels ↓ Ca+ + influx All these make the post synaptic neuron hyperpolarized / more negative/inhibited Net ↑ in anions inside post synaptic neuron hyper polarization ------IPSP  Summation of IPSP Spatial summation Temporal summation Cause inhibition of post synaptic neuron –direct / post synaptic inhibition  Slow EPSP & IPSP Described in autonomic ganglia, Cardiac muscle , Smooth Muscle & cortical neurons Post synaptic potential have long latency:- 100 to 500 ms & lasts several seconds Slow EPSP due to ↓ in K+ conductance Slow IPSP due to ↑ in K+ conductance 5.INACTIVATION OF NT FROM THE SYNAPTIC CLEFT  NT[ neurotransmitter] released in the synaptic cleft from the presynaptic terminal is soon inactivated in one of the following ways: 1. Diffusion of the NT out of the cleft 2. Enzymatic degradation of NT 3. NT reuptake [most of the NT is transported back into the synaptic knob from the synaptic cleft]  6.Generation of the Action Potential in the Postsynaptic Neuron The constant interplay of excitatory and inhibitory activity on the postsynaptic neuron produces a fluctuating membrane potential that is the algebraic sum of the hyperpolarizing and depolarizing activity. The algebraic sum of EPSP’s and IPSP’s on the post synaptic neuron determines the membrane potential. If the summated potential is large enough to depolarize the initial segment to threshold level, then spike potential is generated in the initial segment[as it contains maximum no.of Na+ channels per unit area ]-----which triggers the generation of AP  Properties of synapse One way Sub liminal fringe conduction Synaptic Inhibition Synaptic delay After discharge Convergence Synaptic plasticity Divergence Fatigue Summation Occlusion  1. One way conduction Synapses permit impulse conduction only from pre to post synaptic neuron Because NT is present only in pre synaptic terminal Antidromically conducted impulse dies out after depolarizing cell body One way conduction is necessary for orderly neural function  2. Synaptic delay When an impulse reaches a pre synaptic terminal an interval of at least 0.5 ms occurs before a response is obtained in post synaptic neuron Due to the time taken for the NT to be released from pre synaptic terminal & then act on the post synaptic neuron 3. Convergence Many pre synaptic terminals converge on a single post synaptic neuron Input can be from multiple terminals of same source or from different sources  4. Divergence A single pre synaptic neuron divides into a number of branches & each of these branches can terminate on different post synaptic neurons  5. Summation TEMPORAL SUMMATION SPATIAL SUMMATION Temporal summation- Repeated activity of a synaptic knob in quick succession causing new EPSP before previous EPSP has decayed------ EPSPs summate & reach firing level----- AP results  Spatial summation Instead of repeated stimulation by the same input, 2 or more separate inputs arrive simultaneously at the post synaptic membrane If all the inputs have the same sign,[either all are excitatory or inhibitory], the post synaptic response evoked by all inputs becomes larger than response that would have occurred in response to individual application This type of summation is called spatial summation  Thus, temporal summation occurs when a single presynaptic knob is stimulated repeatedly Spatial summation occurs when many presynaptic knobs converging on one post synaptic neuron are stimulated simultaneously  6. Occlusion When a presynaptic neuron [A] fires , 5 post synaptic neurons discharge When another presynaptic neuron [B] fires , another 5 post synaptic neurons discharge Simultaneous firing of A and B results in activation of 8 post synaptic neurons instead of 10 This is called occlusion  Response to stimulation of A & B together is smaller than the sumof responses to stimulation of A & B separately This decrease in response due to pre synaptic fibers sharing post synaptic neurons is called occlusion  Subliminal fringe Subliminal means below threshold Fringe means border An afferent nerve fiber divides into many branches When afferent neuron is stimulated, the efferent [postsynaptic] neuron which has many presynaptic terminals/knob are excited to threshold level and AP is fired Others which are in the peripheral zone [fringe area] are excited to subthreshold level only, i.e. their excitability is increased but an AP is not fired This is known as subliminal fringe effect 1. When afferent neuron A is stimulated : - There will be depolarization of 5 post synaptic neurons ( efferent neurons) - while 2 efferent neurons are subliminally activated 2. Same with afferent neuron B stimulation 3. When afferent neuron A & B are stimulated at the same time the response is greater than sum of response produced by each separately i.e. 12 motor neurons are stimulated [5+5+2] Subliminal fringe  This is because 2 efferent neurons which are subliminally stimulated both by neuron A and B summate to produce threshold stimulation Due to spatial summation of neurons in common sub liminal fringe 8. Synaptic inhibition 1. Post synaptic inhibition a. Direct inhibition b. Indirect inhibition c. Feedforward inhibition 2. Pre synaptic inhibition  Post synaptic inhibition a. Direct inhibition When synaptic inhibition occurs through formation of IPSP on post synaptic neuron, it is called direct inhibition An inhibitory presynaptic neuron directly inhibits post synaptic neuron by releasing inhibitory NT  This type of inhibition is responsible for reciprocal innervation  Also responsible for golgi tendon organ inhibition [will be taught later] Direct inhibition b. Negative Feed back inhibition / Renshaw cell inhibition / recurrent collateral  inhibition Example of Indirect inhibition Here, neurons may inhibit themselves in a negative feedback fashion. Collateral from spinal motor neuron ends on inhibitory interneuron i.e. renshaw cell In turn , inhibits the discharge of the same motor neuron[renshaw cells liberate an inhibitory NT]  This slows or stops the discharge of motor neuron A collateral from renshaw cell also inhibits neighbouring motor neuron This is called lateral inhibition  c. Feed forward inhibition Seen in cerebellum granule cell excite Purkinje & basket cell[BC] But Basket cell[BC] in turn inhibit Purkinje cell BC acts as inhibitory interneuron Thus, duration of discharge by purkinje cell is reduced & output discharge from purkinje cell is controlled. Pre synaptic inhibition  Mediated by inhibitory neurons that form axo - axonal synapse with excitatory pre synaptic terminal[shown in red colour]  Secrete NT – GABA & cause pre synaptic inhibition  Three mechanisms of pre synaptic inhibition: 1. GABA increases the chloride conductance in the presynaptic membrane through GABAA receptors leading to ↑ Cl- influx ↓ Ca+ + influx ↓ NT release 2. GABA B receptors increase K+ conductance in the presynaptic membrane leading to ↑ K+ efflux ↓ Ca+ + influx ↓ NT release 3. Direct inhibition of NT release independent of Ca+ + influx APPLIED ASPECT: 1. Pre synaptic inhibition is responsible for inhibition of pain transmission in dorsal horn of spinal cord.  Collaterals from ascending touch pathways synapse on inhibitory inter neurons in Spinal cord -----they make axo axonal synapse on pain fibers ------pre synaptic inhibition occurs at the dorsal horn – Substatia Gelatinosa of Rolando (gating of pain) -----so when touch fibers are activated, pain is inhibited  [REFER GATE CONTROL THEORY OF PAIN IN PAIN CHAPTER FOR FURTHER EXPLANATION] 2. Responsible for relaxation of antagonist muscle during contraction of agonist in movements.[reciprocal innervation] 3. Barbiturates facilitate presynaptic inhibition  Significance of synaptic inhibition Helps in accurate movement - in reaching for an object the muscle must be controlled so as not to over shoot the mark  9. Presynaptic facilitation Process by which transmission through a synapse is increased Usually caused by a increase in the NT release from presynaptic terminal  Pre synaptic facilitation Occurs when AP is prolonged & Ca+ + channels are open for a longer time NT at axo axonal synapse is serotonin It increases intra neural cAMP -------phosphorylation of K+ channels ----- closure ----- slow repolarization ------ prolonging the AP-----↑ Ca+ + influx------ ↑NT release  10.Synaptic Fatigue When excitatory synapses are repetitively stimulated at first the no of discharges in post synaptic neuron is great , then progressively becomes less , this is called fatigue Fatigue is a protective mechanism against excess neuronal activity Mechanism of fatigue 1. Mainly exhaustion of NT stores in pre synaptic terminal 2. Progressive inactivation of post synaptic membrane receptors  11.Synaptic plasticity Capability of being easily moulded or changed Synaptic transmission can be increased or decreased for short or long periods on the basis of past experience These changes can occur due to changes in presynaptic or post synaptic areas at the synapses in the brain. Represents forms of learning & memory  Synaptic plasticity  Post tetanic potentiation  Habituation  Sensitization  Long term potentiation  Long term depression  Will be explained in learning and memory chapter in CNS 12.After discharge After discharge is due to the presence of multiple connections b/n the sensory afferent fibers& Motor efferent fibers. Seen in neuronal pools in brain & spinal cord  A single input signal is converted to repetitive discharges as it passes through the synpase & there will be prolonged output discharge from the circuit. Lasts for many millisecs(ms) to min after the input is over  Causes for after discharge:  Synaptic after discharge – long acting NT ( neuropeptide type) is involved  Functions of synapse 1. Impulse transmission 2. Inhibition 3. Integration of 1 impulse with another impulse 4. Learning and memory can be explained in terms of synapse[synaptic plasticity]  IMPORTANT QUESTIONS Synaptic inhibition Synaptic potentials-EPSP,IPSP Properties of synapse Renshaw cell inhibition Presynaptic inhibition Feedforward inhibition is seen in ------------