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USC BISC 307L - Synaptic Transmission Part III
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Synaptic Transmission Part 3Synaptic transmission in the CNS entire surface of the neuron are covered in synapsesEach input weakThus Integration determines overall effectExcitation and inhibition (predominant are inhibitory)Different transmittersWill release different transmitters onto the same neuronThe postsynaptic neuron puts in receptors for different neurotransmittersDifferent receptors for each transmitterOn postsynaptic cellMembrane protein trafficking problemEach transmitter can have multiple receptors also (glutamate has multiple)Ionic and metabolic effectsIntegration of Excitation and Inhibition1. Stimulate Excitatory channel: Increase in permeability of Na+ and permeability of K+Summing up of synaptic activityStimulation is excitatory so depolarizesExample: AMPA type of glutamate receptorOpens a channel that is specific for monovalent cations (Na+ and K+) and when this channel opens it lets Na+ and K+ through so their permeability simultaneously increasesGiven that it has a normal negative resting potential when the synapse is active, Na+ creates a large driving force for Na+ current in to the cell and not as big of a outward K+ current so there is more Na+ coming in causing depolarizationWhere is the critical place where inward current exceeds outward current?Since the distribution of charge is not equal, where the axon comes off of the cell body (axon hillock)(trigger zone) is the point to depolarize because there is a high density of Na+ channels and not as many K+ channels.Trigger zone is the point with the lowest threshold, so closer to AP2. Stimulate inhibitory channel: Increase of Permeability of K+ or increase in permeability of Cl-Stimulating the GABA receptor (inhibitory) produces IPSP*Typically Lysine or GABA are inhibitory neurotransmitters*Hyperpolarize cell by generating outward current through the channels which is carried by either K+ or Cl-A) In case of K+ channel, K+ goes out (more positive that the membrane potential) through the channel generating an outward currentB) In case of Cl- channel, Cl- goes in (more negative potential than the membrane potential) through the channel also generating an outward current3. If trigger both excitatory and inhibitory channelsThere will be an EPSP but it will not be as big because is simultaneously being inhibited by the inhibitory stimulationPosition Contributes to synaptic effectivenessDendrites may contain voltage gated Na+, Ca2+ and K+ channelsWhere they are in the cell mattersFour different synaptic inputs1. Synapse at the axon hillock or trigger zonestrongest effect4. Synapse Dendritic Spineweakest effect because of length constantEfficacy of 1>2>3>4 as positions getting further and further away from the axon hillockThe dendrites, often contain voltage gated Na+,K+,Ca2+ channels- activeThere can actually be action potentials that spread into the dendrites alonePresynaptic inhibition: Another type of inhibitionAxoaxonic synapseStrongly inhibitory effectOpen channels at the end of axon where the current can leak out and not make it to the next neuron due to decrease in Ca2+ concentrationMost powerful type of inhibition of allSynaptic PlasticityPlasticity: Synapses are not static, may change behavior in later time depending on its prior history of activity. Activity dependent behaviorBasis of learning and memory in the nervous systemRecording Neuron activity at synapse through timeThere are 5 types of synapse plasticity1. Facilitation- Short termIf you stimulate the synapse once, in a short period time and you stimulate it again, you get a BIGGER responsePSP gets bigger and bigger every timedecays exponentially if you stop stimulating itThis is called facilitationTakes only milliseconds to build up and decay2. Potentiation-Short termStimulated for longer period of time for longer frequencyEPSPs look like vertical linesJust the same as facilitation for the most part except takes longer to build up (seconds) and takes longer to decayWill facilitate until it plateausFor both facilitation and potentiation the residual calcium hypothesis explains: Every time you stimulate it there is Ca2+ influx and that has to be disposed ofsome diffuses away, some is bound to Ca2+ buffering proteins, some is pumped into mitochondria, or pumped out across the membraneby these mechanisms Ca2+ disappears with time but it does take time so there is a residual amount of Ca2+ with more stimulation that cannot disappear fast enough (doesn’t take that much Ca23 Depression-Short termopposite form of synaptic plasticityif you stimulate it repetitivelyruns down with timemeasured in milliseconds“Depletion of readily releasable neurotransmitter”lots of vesicles in presynaptic terminalsome are not directly there yetof the vesicles inside the transmitter, not all are docked or releasablethere are some that are more ready than otherswhen you stimulate at high frequency you deplete this readily available poolIf you increase the amount of transmitters released then you can get it to depress4. Long term Potentiation (LTP)minutes, hours, dayssynapses that use glutamate as excitatory transmitter. In addition to AMPA (lets Na+ and K+ in) receptor there is another type of receptor called the NMDA (channel that lets Ca2+ in)receptorMakes more receptors for glutamate availableBuild up of potentiation of EPSPBut this persists for minutes to days to months instead of seconds5. Long term depression (LTD)synapses that use glutamate as excitatory transmitter. In addition to AMPA receptor there is another type of receptor called the NMDA receptorCerebellumLike short term depression but longerSound LocalizationPlace and coding neurons to determine sound in spaceTwo ears: sound comes at us as pressure waves. Inputs from the ears (excitatory) come to different array of neurons in the brainIf coming from straight ahead the action potentials from both ears will arrive at the same timeSound from the right ear, will arrive before the same sound from the left ear and you can tell where it comes fromBISC 307L 1st Edition Lecture 8Current Lecture Synaptic Transmission Part 3- Synaptic transmission in the CNSentire surface of the neuron are covered in synapses-o Each input weak Thus Integration determines overall effect Excitation and inhibition (predominant are inhibitory)o Different transmitters Will release different transmitters onto the same neuron The postsynaptic neuron puts in receptors for different neurotransmitterso


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