The Instruction of Sensory Inputs in Inhibitory Circuit Maturation in the Somatosensory Cortex

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PROJECT SUMMARY/ABSTRACT Autism Spectrum Disorders (ASD) are a group of common neurodevelopmental disorders of diverse presentation, though sensory disturbances are consistently noted. Previous work has demonstrated a requirement for sensory input in the morphological maturation of subtypes of interneurons in the somatosensory cortex, but the effect this has on circuit activity and regional output is unknown. We hypothesize that sensory inputs recruit select interneuron subtypes to trigger the maturation of cortical circuits and that perturbations of this process cause lasting abnormalities in regional cortical output, which underlie the pathophysiology of neurodevelopmental disorders. To test our hypothesis, we will record the spontaneous network activity of subpopulations of neurons and in sensory deprived animals. We will identify the presynaptic inputs to these cells with an anatomical tracer. We will also utilize a mouse model of autism to reveal the function of a high-risk ASD gene in the maturation of circuits involving inhibitory interneurons and intracortical projection neurons. This investigation will fill a substantial gap in knowledge of ASD pathogenesis and the interaction between genetic background and activity-dependent developmental processes. The complete picture of ASD pathogenesis remains unclear. This project aims to describe how neuronal activity guides circuit development in the context of increased genetic risk, providing mechanistic insight into disease development and laying the groundwork for earlier diagnosis and novel treatment targets.