Short-term monocular deprivation engages rapid, inhibition-gated ocular dominance plasticity in mouse visual cortex

Ocular dominance (OD) plasticity has long served as a canonical model of experience-dependent cortical plasticity, traditionally thought to be confined to a developmental critical period. Recent human studies, however, show that brief monocular deprivation of just a few hours induces rapid and fully reversible OD shifts, revealing a form of homeostatic plasticity that persists into adulthood. The underlying cellular and circuit mechanisms remain unknown, largely due to the lack of suitable preclinical models. Here, we establish and validate a mouse model of short-term monocular deprivation that closely recapitulates the temporal dynamics observed in humans. Using in vivo electrophysiology in awake mice, we show that two hours of monocular deprivation induce robust yet reversible OD shifts in adult visual cortex, and even larger shifts during the critical period. These shifts are driven by reciprocal modulation of eye-specific cortical responses, with enhanced visual evoked potentials from the deprived eye and concurrent suppression of the non-deprived eye. Chemogenetic manipulation of parvalbumin-positive (PV) interneurons reveals a causal, bidirectional role for PV-mediated inhibition in gating this plasticity: transient PV suppression amplifies OD shifts to juvenile-like levels, whereas PV enhancement constrains or abolishes them. Together, these findings identify a fast, inhibition-gated form of homeostatic OD plasticity operating across developmental stages. This tractable model bridges human perceptual plasticity with defined circuit mechanisms and offers a foundation for developing translational strategies for visual disorders such as amblyopia.