Regulation of dendritic spine activity-dependent structural plasticity

Peter Penzes

Abstract

Structural changes are a key aspect of synaptic plasticity, but the signaling mechanisms which regulate synaptic structural plasticity and coordinate it with functional synaptic plasticity are not well understood. We report that activation of synaptic NMDA receptors in cultured cortical neurons induces dramatic spine morphogenesis and activation of small GTPase Rap1. Rap1 regulates the PDZ domain-containing protein AF-6, which is recruited to the plasma membrane upon Rap1 and NMDA receptor activation. Rap1 and AF-6 regulate spine morphogenesis and mediate NMDA receptor-dependent spine morphogenesis. Rap1 and AF-6 also regulate synaptic localization and clustering of AMPA receptors. We identify a novel signaling pathway which regulates activity-dependent synaptic structural plasticity and coordinates it with functional plasticity.

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