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GABA circuit control of visual cortical plasticity
Takao K. Hensch (RIKEN Brain Science Institute)

26 avril 2005

Our work is focused on how neuronal circuits are sculpted by experience during ’critical periods’ of early postnatal development. After even a brief monocular occlusion in early life, input to visual cortex from the closed eye is functionally weakened then anatomically reduced in size. For the first time, we have achieved a direct control over the timing, duration and consequence of this classical brain plasticity. Gene-targeted deletion of a GABA-synthetic enzyme (GAD65) in mice delays critical period onset indefinitely. Importantly, the key to further understanding lies in our ability to rescue its plasticity with benzodiazepines. Not only can the timing of the critical period now be shifted freely, but also a detailed local circuit analysis of competitive plasticity in vivo is made possible. Indeed, it is paradoxical to think how inhibition might enable plasticity in the developing brain. Our identification of specific GABA circuits that drive critical period onset (large basket cells) and the subsequent sequence of anatomical events (spine pruning) allows for the construction of realistic computational models with which to target the plasticity process further. Two scenarios centered on fast-spiking circuits will be discussed. These findings signal a paradigm shift that considers the balance of excitation-inhibition in cortical plasticity with broad potential relevance across brain systems and for translational research into human development.

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Takao K. Hensch Takao K. Hensch (RIKEN Brain Science Institute)
Laboratory for Neuronal Circuit Development. Professor of neurology at Children’s Hospital Boston and Harvard Medical School. Professor of molecular and cellular biology at Harvard University.