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A01 Molecular mechanisms underlying synaptic plasticity and tenacity

Synaptic plasticity is widely believed to constitute a key mechanism for modifying neuronal network function. However, this hypothesis also implies that synapses, when not driven to change their characteristics by physiologically relevant stimuli, should retain these over time. This project examines mechanisms underlying the long-term persistence of synaptic properties, which we refer to as "synaptic tenacity". We hypothesize that the cytomatrix of the active zone (CAZ) plays fundamental roles in defining, maintaining and regulating synaptic properties over behaviorally relevant long time-scales. We propose to use and expand on experimental and analytical approaches we have previously developed to study the interplay of network activity, synaptic tenacity and synaptic plasticity, and how these depend on, and are regulated by key CAZ components.