Inhibitory threshold for critical-period activation in primary visual cortex

Abstract

Neuronal circuits across several systems display remarkable plasticity to sensory input during postnatal development^{1,2,3,4,5,6,7,8,9,10}. Experience-dependent refinements are often restricted to well-defined critical periods in early life, but how these are established remains mostly unknown. A representative example is the loss of responsiveness in neocortex to an eye deprived of vision^2,3,4,5,6. Here we show that the potential for plasticity is retained throughout life until an inhibitory threshold is attained. In mice of all ages lacking an isoform of GABA (γ-aminobutyric acid) synthetic enzyme (GAD65), as well as in immature wild-type animals before the onset of their natural critical period, benzodiazepines selectively reduced a prolonged discharge phenotype to unmask plasticity. Enhancing GABA-mediated transmission early in life rendered mutant animals insensitive to monocular deprivation as adults, similar to normal wild-type mice. Short-term presynaptic dynamics reflected a synaptic reorganization in GAD65 knockout mice after chronic diazepam treatment. A threshold level of inhibition within the visual cortex may thus trigger, once in life, an experience-dependent critical period for circuit consolidation, which may otherwise lie dormant.