The Electrophysiology and Animal Behavioral (EAB) Core will serve the Center by determining whether synaptic plasticity and behavioral phenotypes in fragile X syndrome (FXS) model mice are corrected by the genetic and pharmacological manipulations described in each project. Examining the electrophysiological aspect of brain function is especially important because synaptic transmission and cellular biophysical properties underlie every aspect of CNS performance in vivo, and plasticity of synaptic function is one of the basic building blocks of neurodevelopment, learning, memory and positive/negative behavioral changes of any sort. Moreover, disruption of cellular physiology and synaptic function is clearly a basis for many forms of neurodevelopmental, neurological, and psychiatric disorders. Examining the behavioral consequences of genetic mutations that cause human neurodevelopmental disorders such as FXS in mice is important not only for understanding the abnormalities caused by the mutations, but also as a means to test whether genetic and pharmacological manipulations can correct and reverse the behavioral abnormalities. Finally, because we are at a watershed moment in understanding the basic molecular biology and role of translational control mechanisms in the function of the CNS, the capacity to study synaptic function and behavior will increasingly become a critical component of many investigators'research programs that are focused on how de novo protein synthesis impacts long-lasting changes in brain function.

Public Health Relevance

This proposal is intended to identify the molecular causes of the Fragile X Syndrome, the most common inherited form of intellectual disability and autism. Novel approaches will be used to determine the impact of genetic and pharmacological manipulations on strains of Fragile X model mice generated by the projects.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Specialized Center--Cooperative Agreements (U54)
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Special Emphasis Panel (ZHD1-DSR-Y (53))
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University of Massachusetts Medical School Worcester
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