Unilateral whisker denervation drives synaptic remodeling across the corpus callosum

Central or peripheral injury cause reorganization of the brain’s connections and functions. A striking change observed after unilateral stroke or amputation is a recruitment of bilateral cortical responses to sensation or movement of the unaffected peripheral area. The mechanisms underlying this phenomenon is described in a mouse-model of unilateral whisker deprivation. Stimulation of intact whiskers yields a bilateral BOLD fMRI response in somatosensory barrel cortex. Whole-cell electrophysiology demonstrated that the intact barrel cortex selectively strengthens callosal synapses to layer 5 neurons in the deprived cortex. These synapses have larger AMPAR and NMDAR mediated events and more GluN2B-containing NMDARs. These factors contribute to a maximally potentiated callosal synapse. This potentiation occludes LTP, which could be rescued to some extent with prior LTD induction. Excitability and E/I balance were altered in a manner consistent with cell-specific callosal changes and support a shift in the overall state of the cortex. This is the first demonstration, to our knowledge, of a cell-specific, synaptic mechanism underlying interhemispheric cortical reorganization.