There is growing consensus that dysfunction of cortico-striatal circuits is a key component of psychiatric illnesses, particularly those that involve abnormalities in incentive-based learning, goal-directed behaviors and habit formation. These dysfunctions reflect changes in network structure and dynamics that likely begin during postnatal development. The goal of this application is to gain insight into the anatomic substrates underlying integration across reward/motivation, cognitive, and motor domains in via cortico-basal ganglia circuits and the early postnatal development of these connections. We have previously demonstrated the convergence of motivation and cognitive circuits via the basal ganglia. In this application, we include the motor system in addition to sampling the entire prefrontal area, creating a comprehensive fronto-striatal connectome. Using computational tools, we will use those results to develop a probabilistic map fronto-striatal connections. In addition, our preliminary results demonstrate that early postnatal myelin development varies not only in frontal grey matter areas, but also between layer within areas. We will build on these results to evaluate postnatal development of frontal inputs to the ventral striatum.
Aim 1 combines conventional tracing experiments with computational tools to develop a complete map of fronto-striatal connections, identifying areas in which fiber from diverse functional regions of cortex converge in the striatum.
Aim 2 will examine postnatal myelin expansion during early postnatal development compared to adult animals.
Aim 3 will bring together results from Aims 1 & 2 to determine potential changes in FC-striatal connectivity and its relationship to cortical myelin expansion during early postnatal development.
There is growing consensus that dysfunction of cortico-striatal circuits is a key component of psychiatric illnesses. Moreover, there is compelling evidence that points to neurodevelopmental origins for most psychiatric disorders. This study will examine the anatomical underpinnings of functional integration through the cortico-striatal neural network and changes in its circuitry during early postnatal development.
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