Synapse-Selective Control of Cortical Maturation and Plasticity by Parvalbumin-Autonomous Action of SynCAM 1

Abstract

Summary: Cortical plasticity peaks early in life and tapers in adulthood, as exemplified in the primary visual cortex (V1), wherein brief loss of vision in one eye reduces cortical responses to inputs from that eye during the critical period but not in adulthood. The synaptic locus of cortical plasticity and the cell-autonomous synaptic factors determining critical periods remain unclear. We here demonstrate that the immunoglobulin protein Synaptic Cell Adhesion Molecule 1 (SynCAM 1/Cadm1) is regulated by visual experience and limits V1 plasticity. Loss of SynCAM 1 selectively reduces the number of thalamocortical inputs onto parvalbumin (PV+) interneurons, impairing the maturation of feedforward inhibition in V1. SynCAM 1 acts in PV+ interneurons to actively restrict cortical plasticity, and brief PV+-specific knockdown of SynCAM 1 in adult visual cortex restores juvenile-like plasticity. These results identify a synapse-specific, cell-autonomous mechanism for thalamocortical visual circuit maturation and closure of the visual critical period. : Ribic et al. show that cortical plasticity is actively restricted by the synapse-organizing molecule SynCAM 1. The protein acts in parvalbumin interneurons to recruit excitatory thalamocortical terminals. This controls the maturation of inhibition and actively limits cortical plasticity, revealing a synaptic locus for closure of cortical critical periods. Keywords: synapse, SynCAM, Cadm, visual cortex, critical period, plasticity, parvalbumin, thalamocortical inputs