Nogo receptor 1 confines a disinhibitory microcircuit to the critical period in visual cortex

Abstract

A characteristic of the developing mammalian visual system is a brief interval of plasticity, termed the “critical period,” when the circuitry of primary visual cortex is most sensitive to perturbation of visual experience. Depriving one eye of vision (monocular deprivation [MD]) during the critical period alters ocular dominance (OD) by shifting the responsiveness of neurons in visual cortex to favor the nondeprived eye. A disinhibitory microcircuit involving parvalbumin-expressing (PV) interneurons initiates this OD plasticity. The gene encoding the neuronal nogo-66-receptor1(ngr1/rtn4r) is required to close the critical period. Herewecombinedmousegenetics, electrophysiology,andcircuitmapping with laser-scanning photostimulation to investigate whether disinhibition is confined to the critical period by ngr1.We demonstrate that ngr1 mutant mice retain plasticity characteristic of the critical period as adults, and that ngr1 operates within PV interneurons to restrict the loss of intracortical excitatory synaptic input following MD in adult mice, and this disinhibition induces a “lower PV network configuration” in both critical-period wild-type miceandadult ngr1-/- mice.Wepropose that ngr1 limits disinhibition to close the critical period forODplasticityand that a decrease in PV expression levels reports the diminished recent cumulative activity of these interneurons.