Inhibitory threshold for critical-period activation in primary visual cortex

Neuronal circuits across several systems display remarkable plasticity to s ensory input during postnatal development(1-10) Experience-dependent refine ments are often restricted to well-defined critical periods in early life, but how these are established remains mostly unknown. A representative exam ple is the loss of responsiveness in neocortex to an eye deprived of vision (2-6). Here we show that the potential for plasticity is retained throughou t life until an inhibitory threshold is attained. In mice of all ages lacki ng an isoform of GABA (gamma-aminobutyric acid) synthetic enzyme (GAD65), a s well as in immature wild-type animals before the onset of their natural c ritical period, benzodiazepines selectively reduced a prolonged discharge p henotype to unmask plasticity. Enhancing GABA-mediated transmission early i n life rendered mutant animals insensitive to monocular deprivation as adul ts, similar to normal wild-type mice. Short-term presynaptic dynamics refle cted a synaptic reorganization in GAD65 knockout mice after chronic diazepa m treatment. A threshold level of inhibition within the visual cortex may t hus trigger, once in life, an experience-dependent critical period for circ uit consolidation, which may otherwise lie dormant.