NSC 4352 1st Edition Exam 4 Study Guide Lectures 18 20 Lecture 18 Synaptic Plasticity Key Variables that characterize quantal vesicular release the number of release sites N the probability of quantal release p the size of the quantal response d Synaptic Facilitation increase in synaptic strength that results when action potentials occur in rapid succession result of prolonged calcium elevation residual calcium hypothesis target of action is likely synaptotagmin Synaptic Depression reduction in synaptic strength during successive action potentials results from progressive depletion of vesicle pool Lecture 19 Synaptic Plasticity II Plasticity on longer time scales Long term potentiation LTP LTP shares many features with long term memory making it an attractive candidate for a cellular mechanism of learning Both LTP and long term memory are triggered rapidly each depends upon the synthesis of new proteins each has properties of associativity and each can last for many months Model for the induction and maintenance of early LTP Model for induction maintenance of late LTP the and NMDAR dependent LTP is the best understood form of long lasting synaptic plasticity in the mammalian brain It requires the activation of NMDARs by presynaptically released glutamate while the postsynaptic membrane is significantly depolarized 2 2 Depolarization relieves the voltage dependent block of the NMDAR by Mg allowing Ca to enter 2 The rise in postsynaptic Ca concentration activates intracellular signaling cascades that include several protein kinases most notably CaMKII and PKC The primary mechanisms underlying the increase in synaptic strength during early LTP is a change in AMPAR phosphorylation increased conductance and AMPAR trafficking resulting in an increased number of AMPARs in the postsynaptic plasma membrane with no effect on NMDARs Within a few hours the maintenance of late LTP requires synthesis of new proteins LTP is accompanied by enlargements of dendritic spines and associated postsynaptic densities which may represent the morphological correlate of information storage following LTP induction at synapses Lecture 20 Spike Timing Dependent Plasticity STDP is a temporally asymmetric form of Hebbian learning induced by tight temporal correlations between the spikes of pre and postsynaptic neurons In a typical STDP protocol a synapse is activated by stimulating a presynaptic neuron or presynaptic pathway shortly before or shortly after making the postsynaptic neuron fire an action potential The pairing is repeated for 50 100 times at a fixed frequency e g at 0 1 Hz The change of the synaptic weight the amplitude or slope of the EPSP or IPSP is plotted as a function of the relative timing between presynaptic spike arrival and postsynaptic firing The general rule of STDP If an input EPSP to a neuron occurs on average immediately before that neuron s output spike then that input is potentiated LTP pre before post If an input EPSP occurs immediately after an output spike then that input becomes weaker LTD post before pre STDP encodes causality Inputs that contribute to spiking in the postsynaptic neuron are reinforced while inputs that are not causing the neuron to spike are made less likely to contribute in the future