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Science 303 (5664): 1681-1683

Copyright © 2004 by the American Association for the Advancement of Science

Specific GABAA Circuits for Visual Cortical Plasticity

Michela Fagiolini,1 Jean-Marc Fritschy,2 Karin Löw,2 Hanns Möhler,2,3 Uwe Rudolph,2 Takao K. Hensch1*

Abstract: Weak inhibition within visual cortex early in life prevents experience-dependent plasticity. Loss of responsiveness to an eye deprived of vision can be initiated prematurely by enhancing {gamma}-aminobutyric acid (GABA)–mediated transmission with benzodiazepines. Here, we use a mouse "knockin" mutation to {alpha} subunits that renders individual GABA type A (GABAA) receptors insensitive to diazepam to show that a particular inhibitory network controls expression of the critical period. Only {alpha}1-containing circuits were found to drive cortical plasticity, whereas {alpha}2-enriched connections separately regulated neuronal firing. This dissociation carries implications for models of brain development and the safe design of benzodiazepines for use in infants.

1 Laboratory for Neuronal Circuit Development, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako-shi, Saitama, 351-0198 Japan.
2 Institute of Pharmacology and Toxicology, University of Zürich, Winterthurerstrasse 190, Zurich, CH-8057 Switzerland.
3 Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology (ETH), Winterthurerstrasse 190, Zürich, CH-8057 Switzerland.

* To whom correspondence should be addressed. E-mail: hensch{at}

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