title: 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. 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. 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 (gamma-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.
authors.affiliation: Laboratory for Neuronal Circuit Development, Brain Science Institute RIKEN, Saitama, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Fagiolini
authors.forename: T K
authors.initials: TK
authors.lastname: Hensch
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D003423:Critical Period, Psychological; D003975:Diazepam / Q000008:administration & dosage; D000882:Haplorhini; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009473:Neuronal Plasticity / Q000187:drug effects; D012683:Sensory Deprivation; D014793:Visual Cortex / Q000187:drug effects / Q000502:physiology*; D014796:Visual Perception / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D005680:gamma-Aminobutyric Acid; D003975:Diazepam