The brains's basal ganglia are involved in the control of motor and cognitive functions. The striatum, their primary input structure, receives excitatory, glutamatergic input from virtually the entire cortex. The striatum is composed of two histochemically and connectionally distinct compartments, the patch (or striosome) and matrix regions. In the adult rat, the cortical inputs to the striatum are segregated such that deep-layer cortical cells, particularly those from the pre-limbic areas, project primarily to the patch neurons, and superficial-layer cortical cells, particularly those from the agranular motor regions, project primarily to the matrix neurons. The mechanisms by which different inputs from the cortex segregate into the patch and matrix compartments are not known. The goal of this research planning grant is to provide a foundation for studying the mechanisms underlying the segregation of cortical afferents to the patch and matrix compartments within the mouse striatum. To accomplish this goal, the developmental time course of the cortical inputs to the mouse striatum will be determined. It is hypothesized that axons from mouse cortical neurons of the deep and superficial layers first project homogeneously throughout the striatum and only later restrict themselves to the patch and matrix compartments. This hypothesis will be tested by using a fluorescent carbocyanine dye to trace cortical axons to the patch and matrix regions of the striatum in the developing and adult mouse. The mouse will be used in these experiments to facilitate future studies employing genetic manipulation of the glutamate system. These results will lay the foundation for a series of experiments investigating the overall hypothesis that glutamate, acting through NMDA receptors, influences the segregation of corticostriatal innervation into the patch and matrix compartments.
