Synapse-selective control of cortical maturation and plasticity engages an interneuron-autonomous synaptic switch

Highlights The synaptogenic molecule SynCAM 1 is selectively regulated by visual experience SynCAM 1 controls thalamic input onto cortical Parvalbumin (PV + ) interneurons PV + -specific knockdown of SynCAM 1 arrests maturation of cortical inhibition Thalamic excitation onto PV + interneurons is essential for critical period closure eTOC Blurb Ribic et al. show that network plasticity in both young and adult cortex is restricted by the synapse organizing molecule SynCAM 1. On a cellular level, it functions in Parvalbumin-positive interneurons to recruit thalamocortical terminals. This controls the maturation of inhibitory drive and restricts plasticity in the cortex. These results reveal the synaptic locus of cortical plasticity and identify the first cell-autonomous synaptic factor for closure of cortical critical periods. Summary Brain plasticity peaks early in life and tapers in adulthood. This is exemplified in the primary visual cortex, where brief loss of vision to one eye abrogates cortical responses to inputs from that eye during the critical period, but not in adulthood. The synaptic locus of critical period plasticity and the cell-autonomous synaptic factors timing these 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 visual cortex plasticity. SynCAM 1 selectively controls the number of excitatory thalamocortical (TC) inputs onto Parvalbumin (PV + ) interneurons and loss of SynCAM 1 in turn impairs the maturation of TC-driven feed-forward inhibition. SynCAM 1 acts in cortical PV + interneurons to perform these functions and its PV + -specific knockdown prevents the age-related plasticity decline. These results identify a synapse type-specific, cell-autonomous mechanism that governs circuit maturation and closes the visual critical period.