Disinhibition is an obligatory initial step in the remodeling of cortical circuits by sensory experience, yet the underlying mechanisms remain unclear. Our investigation of mechanisms for disinhibition in the classical model of ocular dominance plasticity (ODP) uncovered an unexpected novel form of experience-dependent circuit plasticity. In layer 2/3 of mouse visual cortex monocular deprivation triggers an ”all-or-none” elimination of approximately half the connections from local pyramidal cells onto parvalbumin-positive interneurons (Pyr[->]PV), without affecting the strength of the remaining connections. This loss of Pyr[->]PV connections is transient, lasting one day only, has a critical period commensurate with the ODP critical period, and is contingent on a reduction of neuropentraxin2 (NPTX2), which normally stabilizes Pyr[->]PV connections. Bidirectional manipulations of NPTX2 functionality that prevent/promote the elimination Pyr[->]PV connections also promote/prevent ODP. We surmise, therefore, that this rapid and reversible loss of local Pyr[->]PV circuitry gates experience-dependent cortical plasticity.
bioRxiv Subject Collection: Neuroscience