advancing research in basic sciences and mathematics
Recent work has demonstrated that autism spectral disorder (ASD) results from both genetic and environmental influences. Less clear is physiological basis underlying ASD at a cellular level. Given the prevalence of epilepsy in ASD and the known linkage of genes involved in mediating cortical inhibition in the nervous system, an appealing hypothesis is that failure inhibitory signaling is a major cause of ASD. My laboratory studies the genetic origins of cortical interneurons. We believe that misspecification of subclasses of cortical interneurons may be a prevalent cause of ASD. To explore this possibility, we have identified genes that are utilized during development in the generation of specific subclasses of interneurons and propose here to create mouse models of ASD by the disruption of genes we believe will alter cortical interneuron diversity. Using genetic methods, we will study how the loss of these genes affects the development of specific subtypes of cortical interneurons and examine the consequences on cortical circuitry and behavior that result from these changes. An aspect of this work that makes it particularly attractive as a means to study ASD is that a number of the genes we will study have either been linked to ASD (such as, Cacnb4 and Caspr4), or molecularly interact with genes implicated in this disorder, such as neuroligin. We hope by taking a prospective approach of creating mice with genetic defects that affect the balance of excitation and inhibition in the brain, we will take the first steps in providing a bona fide animal model for studying ASD.
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