Neurons acquire multiple functional properties through an experience-dependent development during a limited time in early postnatal life (“critical periods”). Our research focuses on understanding the mechanisms underlying this fundamental process by combining molecular techniques with electrophysiological and behavioral analysis of systems level phenomena in vivo. At Children’s Hospital Boston, we concentrate on elucidating the interaction between environment and epigenetic mechanisms in the etiology of autism spectrum disorders (ASDs). Major insight was provided by the discovery that 80% of classical Rett’s Syndrome, a leading cause of mental retardation with autistic features, is caused by mutations that affect the methyl-CpG-binding protein, MeCP2, directly implicating an epigenetic pathway in the complex behavioral phenotype of ASDs. Little, however, is known if and how sensory-experience affects specific brain functions through epigenetic mechanisms. An ideal model to study experience-dependent plasticity is the visual system. During the past years, we achieved the first direct control over critical period timing by manipulating a specific subset of local inhibitory circuits. One unexpected outcome of our approach has been the discovery that experience-dependent development of different receptive field properties may be mediated by distinct molecular mechanisms. Our goal is to reveal the reciprocal relationship of chromatin status to excitatory/inhibitory circuit balance that underlies healthy brain development and potential therapeutic strategies for reactivating plasticity in adulthood.
|
References:
Fagiolini M, Pizzorusso T, Berardi N, Domenici L, Maffei. Functional postnatal development of the rat visual cortex. Vision Res 1994;34:709-720.
Antonini A, Fagiolini M, Stryker MP. Anatomical correlates of functional plasticity in mouse visual cortex. J Neurosci 1999;19:4388-4406.
Fagiolini M, Hensch TK. Inhibitory threshold for critical-period activation in primary visual cortex. Nature 2000;404:183-186.
Fagiolini M, Katagiri H, Miyamoto H, Mori H, Grant SGN, Mishina M, Hensch TK. Separable features of visual cortical plasticity revealed by N-methyl-D-aspartate receptor 2A signaling. Proc Natl Acad Sci USA 2003;100:2854-2859.
Fagiolini M, Fritschy J-M, Löw K, Möhler ., Rudolph U, Hensch TK. Specific GABAA circuits for visual cortical plasticity. Science 2004; 303:1681-1683. |
Harvard University Home / GSAS Home / HMS Home