NSC 4352 1st EditionExam # 4 Study Guide Lectures: 18-20Lecture 18: Synaptic PlasticityKey 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 synaptotagminSynaptic Depression: reduction in synaptic strength during successive action potentials•results from progressive depletion of vesicle poolLecture 19: Synaptic Plasticity IIPlasticity 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 LTPModel for the induction and maintenance of late LTPNMDAR-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.Depolarization relieves the voltage-dependent block of the NMDAR by Mg2+, allowing Ca2+ to enter. The rise in postsynaptic Ca2+ 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 firingThe 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