My work is dedicated in understanding the mechanisms underlying experience-dependent visual circuit development and refinement during early postnatal life in health and neurodevelopmental disorder using multidisciplinary approaches that include molecular, cellular, electrophysiological and behavioral analysis. Specifically, we have utilize the visual system as our model system and have identified a visual phenotype in mouse model of Rett Syndrome and demonstrated its rescue by environmental and genetic manipulation. These results have paved the way to the identification of a specific role for MeCP2 in the experience-dependent refinement of cortical circuits by regulating the excitation of pivotal inhibitory neurons. The identification of a particular receptor pathway within a specific cortical circuit now offers an accessible membrane target for drug intervention strategies. These initial findings strongly suggested that visual processing in RTT patients may be altered and can be used as a robust biomarker of both cortical status and its response to therapy. To this end, in collaboration with the Rett Clinic at Boston Children’s Hospital and the laboratory of Cognitive Neuroscience, we assessed the cortical function of the visual system in young girls with RTT using visual evoked potentials (VEP) as previously done in MeCP2 mutant mice Remarkably, we found significant differences between typically developing children and RTT patients supporting the introduction of standardized VEP analysis in clinical and research settings to probe the neurobiological mechanism underlying functional impairment and to longitudinally monitor progression of the disorder and response to treatment. We are now testing the impact of arousal on visual processing in disorder and the establishment of additional novel and robust biomarkers.
