BISC 307L 1st Edition Lecture 8 Current Lecture Synaptic Transmission Part 3 Synaptic transmission in the CNS entire 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 neurotransmitters o Different receptors for each transmitter On postsynaptic cell Membrane protein trafficking problem Each transmitter can have multiple receptors also glutamate has multiple o Ionic and metabolic effects Integration of Excitation and Inhibition o 1 Stimulate Excitatory channel Increase in permeability of Na and permeability of K Summing up of synaptic activity Stimulation is excitatory so depolarizes Example AMPA type of glutamate receptor Opens 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 increases Given 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 depolarization Where 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 AP o 2 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 current B In case of Cl channel Cl goes in more negative potential than the membrane potential through the channel also generating an outward current o 3 If trigger both excitatory and inhibitory channels There will be an EPSP but it will not be as big because is simultaneously being inhibited by the inhibitory stimulation Position Contributes to synaptic effectiveness o Dendrites may contain voltage gated Na Ca2 and K channels o Where they are in the cell matters o Four different synaptic inputs 1 Synapse at the axon hillock or trigger zone strongest effect 4 Synapse Dendritic Spine weakest effect because of length constant Efficacy of 1 2 3 4 as positions getting further and further away from the axon hillock o The dendrites often contain voltage gated Na K Ca2 channels active o There can actually be action potentials that spread into the dendrites alone o Presynaptic inhibition Another type of inhibition Axoaxonic synapse Strongly inhibitory effect Open 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 concentration Most powerful type of inhibition of all Synaptic Plasticity o Plasticity Synapses are not static may change behavior in later time depending on its prior history of activity Activity dependent behavior o Basis of learning and memory in the nervous system o Recording Neuron activity at synapse through time o There are 5 types of synapse plasticity 1 Facilitation Short term If you stimulate the synapse once in a short period time and you stimulate it again you get a BIGGER response PSP gets bigger and bigger every time decays exponentially if you stop stimulating it This is called facilitation Takes only milliseconds to build up and decay 2 Potentiation Short term Stimulated for longer period of time for longer frequency EPSPs look like vertical lines Just the same as facilitation for the most part except takes longer to build up seconds and takes longer to decay Will facilitate until it plateaus For 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 Ca2 3 Depression Short term opposite form of synaptic plasticity if you stimulate it repetitively runs down with time measured in milliseconds Depletion of readily releasable neurotransmitter lots of vesicles in presynaptic terminal some are not directly there yet of the vesicles inside the transmitter not all are docked or releasable there are some that are more ready than others when you stimulate at high frequency you deplete this readily available pool If you increase the amount of transmitters released then you can get it to depress 4 Long term Potentiation LTP minutes hours days synapses 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 receptor Makes more receptors for glutamate available Build up of potentiation of EPSP But this persists for minutes to days to months instead of seconds 5 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 receptor Cerebellum Like short term depression but longer Sound Localization o Place and coding neurons to determine sound in space o Two ears sound comes at us as pressure waves Inputs from the ears excitatory come to different array of neurons in the brain o If coming from straight ahead the action potentials from both ears will arrive at the same time Sound from the right ear will arrive before the same sound from the left ear and you can tell where it comes from