Synapses differ markedly in their performance, even amongst those on a single neuron. The mechanisms that drive this functional diversification are of great interest because they enable adaptive behaviors and are targets of pathology. Considerable effort has focused on elucidating mechanisms of plasticity that involve changes to presynaptic release probability and the number of postsynaptic receptors. However, recent work is clarifying that nanoscale organization of the proteins within glutamatergic synapses impacts synapse function. Specifically, active zone scaffold proteins form nanoclusters that define sites of neurotransmitter release, and these sites align transsynaptically with clustered postsynaptic receptors. These nanostructural characteristics raise numerous possibilities for how synaptic plasticity could be expressed.
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