SENSORY EXPERIENCE SCULPTS INHIBITORY CIRCUIT ORGANIZATION THROUGH CELL-TYPE-SPECIFIC MOLECULAR INTERACTION PROGRAMS

Sensory experience is required for the proper maturation of cortical inhibitory circuits, but the molecular mechanisms linking experience to inhibitory connectivity remain unclear. Using chronic bilateral enucleation in the mouse visual system as a model of persistent sensory deprivation, combined with single nucleus transcriptomics, we dissected experience dependent gene regulation in inhibitory neurons across development. We identify two modes of experience dependent regulation: shared transcriptional programs reflecting global maturation, and cell type specific programs enriched for cell surface and junctional molecules, suggesting a role in shaping connectivity rather than general neuronal identity. Leveraging cell to cell communication analysis, we show that sensory deprivation selectively disrupts inhibitory interaction programs in a cell type specific manner, revealing altered molecular connectivity logic within inhibitory networks. These findings establish a molecular framework linking sensory experience to inhibitory circuit organization and provide a resource of experience dependent genes and interaction programs underlying cortical plasticity.