Augmenting AMPA receptor signaling following spinal cord injury increases ependymal-derived stem/progenitor cell (epNSPC) migration and promotes functional recovery
Using lineage tracing in adult mice, we demonstrate that pharmacological blockade of AMPARs reduces epNSPC proliferation and migration after cervical SCI. Similarly, knocking out AMPAR subunits in Foxj1+ ependymal cells and their progeny abolishes glutamate-mediated AMPA currents and impairs the migration of epNSPCs after SCI. Augmenting AMPAR signaling with ampakines maintains the acute maturation reversal  of epNSPCs into the chronic injury period, enhances ependymal-glial cell contacts, which may contribute to the spatial distribution and migratory pattern of activated ependymal cells, ameliorates the decrease in corticospinal tract excitability subacutely after SCI, and improves long-term neurobehavioral recovery. Together this work uncovers a neurotransmitter receptor-dependent  mechanism of epNSPC activation following injury, which may be targeted to harness the regenerative potential of the spinal cord. Overall design: Single nucleus RNA sequencing