Memory, Learning, and Synaptic Plasticity

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Hypothesis 1: Memory is stored as strengths of synaptic connections in neural circuits

synaptic weight matrices can in principle store enormous amounts of information that can be used to transform specific input patterns to specific output patterns (memory recalls)

axons that project from neurons in the superficial layers of the entorhinal cortex, which constitute the perforant path, synapse onto the dendrites of granule cells in the dentate gyrus, the input part of the hippocampus.

Hypothesis 2: Learning modifies the strengths of synaptic connections

Hebb's rule!

synaptic plasticity: used to describe changes of the strengths of synaptic connections in response to experience and neuronal activity

Long term potentiation of synaptic efficacy can be induced by HFS

experiment: extracellular recording electrode was implanted in the dentate gyrus to record the activity of granule cell populations near the electrode. stimulating electrode was placed in the perforant path to provide snaptic input to the granule cells. single stimulus applied to the stimulating electrode would depolarize the granule cell populations via the perforant path --> granule cell synapses. This was recorde as a fEPSP, whose amplitude is a measure of the strength of synaptic transmission b/w the stimulated axons of the perforant path and the granule cell population near the recording electrode.

LTP at the hippocampal CA3 --> CA1 synapse exhibits input specificity, cooperativity, and associativity

specificity: occurs at the synapses that have experienced HFS but doesnt occur at inactive synapses of the same postsynaptic neuron

coop: LTP is induced when the presynaptic cell fires and releases NTs AND the postsynaptic cell is depolarized

associativity: if b receives a weak stimulus during the PS is depolarized and there is really high freq stimulation, the synapses a and b get potentiatied

NMDA receptor is a coincidence detector for LTP induction

opening of the NMDA receptor channel requires simultaneous glutamate release from the presynaptic terminal and depolarization of the postsynaptic neuron to remove the blockage by Mg. this accounts for coop and assoc.

Recruitment of AMPA receptors to the postsynaptic surface is the predominant mechanism of LTP expression

two hypotheses: a presynaptic mechanism involving an increase in the probability that action potential arrival triggers NT release, and a postsnatic mechanism involving an increase in the sensitivity of the postsynaptic cell to the release of the same amount of NT.

following activation of the NMDA receptor during LTP induction, more ampa receptors are inserted on the post synaptic membrane. glutamate release can trigger the opening of more ampa receptors and hence, stronger depolarization.

what are silent synapses? well, some glutamate synapses only contain NMDA receptors on postsynap surfface. these can't be activated by presynaptic glutamate release alone. however, coincident postsyn depolarization (through AMPAr at other synapses) and glutamate release activate the NMDA receptors into postsyn membrane, transforming silent synapses into synapses that can be activated by presynaptic activity alone.

LTP expression involves both the activation of silent synapses and an increased number of AMPAr in synapses that already have AMPA receptors.

Long term depression weakens synaptic efficacy

LTD function is dependent of the NMDA receptor and calcium influx. the increase of calcium resulting from low frequency stimulation is lower than that resulting from HFS. THIS lower increase of ca is thought to preferentially activate ca-dependent phosphatases, which do the opposite of what LPTP-actvated kinases do: the phosphates reduce the number of AMPA receptors at the postsynaptic plasma membrane so that subsequent glutamate releease from the presynaptic terminal induces a smaller depolarization.

Spike timing dependent plasticity can adjust synaptic efficacy bidirectionally

STDP:precise timing of pre and post synaptic firing is critical in determining the sign of the synaptic strength change

if pre fires before post within a narrow window , and repeated, efficacy increases. pre after post is ineffective.

long lasting changes of connection strengths involve formation of new synapses

long lasting changes depend on new gene expression usually.