Upregulation of Calbindin in Adult Inhibitory Neurons Reactivates Critical Period Plasticity in Mouse Visual Cortex

Critical periods are windows of peak learning performance where heightened synaptic plasticity enables fast, robust reorganization in juvenile brain circuits. Unlike adult plasticity which requires ongoing, persistent change in sensory experience, cortical representations can be rapidly changed during critical periods and have enduring effects. Transplantation of GABAergic inhibitory neurons has been shown to restore critical period plasticity to recipient circuits by triggering signalling changes within host inhibitory neurons. Here we transcriptionally profiled host inhibitory neurons in mouse primary visual cortex (V1) to detect gene expression changes during transplant-induced plasticity. Gene ontology enrichment analysis of differentially-expressed (DE) transcripts in host inhibitory neurons revealed synaptic plasticity- and inhibitory neuron development-related profiles. We assessed the protein expression of a top DE candidate, the calcium-binding protein Calbindin (Calb1), across transplant conditions and developmental stages. We found high Calb1 expression during the V1 critical period and during transplant-induced plasticity. To assess the functional significance of transplant-reactivated DE gene activity on visual cortical plasticity, we developed a set of AAVs to manipulate Calb1 expression specifically within inhibitory neurons. Using intrinsic signal imaging to measure ocular dominance plasticity, we found that Calb1 levels in V1 inhibitory neurons determine the extent of visual cortical plasticity. Our study provides evidence that direct induction of critical period-stage gene expression patterns in inhibitory neurons restores juvenile plasticity in targeted adult cortical circuits.