Subsynaptic spatial organization as a regulator of synaptic strength and plasticity

Abstract

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.

Figure 1

Key synaptic proteins are enriched within nanocolumns. High density nanoclusters of RIM1/2 and (M)Unc13 dictate sites of vesicle fusion following action potentials, which are assembled in alignment with postsynaptic nanoclusters of receptors [2**,8**]. The coupling between the release and receptors through transsynaptic proteins together with the distributions of proteins in grey is hypothetical, while the distributions of color-coded proteins have been confirmed. Adapted from [2**].

Figure 2

Potential mechanisms of synaptic plasticity mediated by changes in release-receptor alignment. These changes may arise from repositioning or change in the number or position of release sites presynaptically, from altering the number, position, size, or internal density of postsynaptic receptor clusters, or from changing the nature of transsynaptic coupling. Panels with notations depict mechanisms that have support from direct or indirect evidence in the literature.