Structural and Molecular Remodeling of Dendritic Spine Substructures during Long-Term Potentiation

Synapses store information by long-lasting modifications of their structure and molecular composition, but the precise chronology of these changes has not been studied at single-synapse resolution in real time. Here we describe the spatiotemporal reorganization of postsynaptic substructures during long-term potentiation (LTP) at individual dendritic spines. Proteins translocated to the spine in four distinct patterns through three sequential phases. In the initial phase, the actin cytoskeleton was rapidly remodeled while active cofilin was massively transported to the spine. In the stabilization phase, cofilin formed a stable complex with F-actin, was persistently retained at the spine, and consolidated spine expansion. In contrast, the postsynaptic density (PSD) was independently remodeled, as PSD scaffolding proteins did not change their amount and localization until a late protein synthesis-dependent third phase. Our findings show how and when spine substructures are remodeled during LTP and explain why synaptic plasticity rules change over time. •Postsynaptic proteins are reorganized during LTP in three sequential phases•Cofilin is rapidly, persistently enriched in the spine via a stable F-actin complex•Cofilin signaling pathway is necessary for the maintenance of spine expansion•Delayed PSD growth is spine expansion independent but protein synthesis dependent Bosch et al. describe the spatiotemporal reorganization of postsynaptic substructures during potentiation at single dendritic spines. They uncover the late-phase growth of the postsynaptic density and the unique dynamics of cofilin, which play a critical role in consolidating spine growth.