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Inhibitory threshold for critical-period activation in primary visual cortex

Abstract

Neuronal circuits across several systems display remarkable plasticity to sensory input during postnatal development1,2,3,4,5,6,7,8,9,10. 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 vision2,3,4,5,6. 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.

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Figure 1: GAD65 knockout (KO) mice can express experience-dependent plasticity throughout life.
Figure 2: Diazepam reduces integrated field response and prolonged discharge.
Figure 3: Enhancement of intracortical inhibition triggers plasticity in young but not adult wild-type mice.
Figure 4: Early enhancement of inhibitory transmission restores a critical period and STD to GAD65 knockout mouse visual cortex.

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Acknowledgements

We thank K. Hartman for contributing to Fig. 4c, N. Mataga for comments, and S. Fujishima for genotyping and maintenance of the GAD65 mouse colony re-derived from original heterozygote breeding pairs which were kindly provided by S. Baekkeskov and S.F. Kash.

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Correspondence to Takao K. Hensch.

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Fagiolini, M., Hensch, T. Inhibitory threshold for critical-period activation in primary visual cortex. Nature 404, 183–186 (2000). https://doi.org/10.1038/35004582

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