Molecular Control of Long-Range Fronto-Posterior Cortical Projection Maturation Mediating Attention

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Project Summary Neuropsychiatric disorders with developmental origins affect more than 15% of children in the United States and poses a major public health concern requiring $35 billion a year to address in large part due to secondary disability. Clinical efforts to diagnose, treat, and monitor disease have been hindered because they rely on observations of non-specific clusters of symptoms, thus limiting current pharmacologic therapeutics to symptom management. Initial studies report that distal cortical areas fail to connect in these disorders, however, the development of more effective pharmacological interventions requires a better basic understanding of normal maturation and implicated pathophysiology. These processes can be examined in mice. Such work in our lab has identified a necessary driver of maturation—Lynx1— for a projection commonly impaired from the frontal cortex to the visual cortex that mediates visual attention processing. This proposal seeks to more fully examine how Lynx1 promotes normal neural development in this key cortical connection and will investigate the functional and structural consequences of aberrant development in the absence of this important molecule. I hypothesize that Lynx1, an endogenous nicotinic receptor inhibitor, regulates the integration of this projection into forming neural networks that enact visual attention. This pathophysiological insight will promote the development of more effective diagnosis and targeted therapies for neurodevelopmental disorders.