The function of the basal ganglia and, in particular, striatum, the basal ganglia structure in which dopamine exerts a predominant influence, is poorly understood. Consequently, what dopamine does in the basal ganglia remains a fundamentally unanswered question. The broad objective of this research is to elucidate these functions. It is known that striatum comprises neurochemically and, apparently, functionally distinct, interdigitating cellular compartments that have distinct connections with other parts of the brain. Understanding striatal function would appear to depend, at least in part, upon understanding the influences that dopamine exerts on systems traversing these cellular domains. Two compartments, patch (striosome) and matrix, have been identified in dorsal striatum. The compartmentation in ventral striatum is less defined, but shell and core subterritories in the nucleus accumbens region recently have been considered as fundamental units of organization. While it has been shown that patch and matrix receive morphologically distinct mesostriatal dopamine projections, it is not known whether there is compartmentation of the dopamine innervation in the accumbens. To address whether subsets of meso-accumbal dopamine fibers observe subterritorial boundaries in the accumbens, an experiment has been designed to determine if neurochemically distinct subterritories in the accumbens are selectively innervated by distinct subpopulations of ventral mesencephalic neurons. Insofar as multiple postsynaptic avenues for the distribution of dopamine influences must exist in the striatum, distinct, histochemically detectable responses of striatal neurons to distinct perturbations of dopaminergic neurotransmission will be investigated. Two subtypes of striatal neurons that accumulate neurotensin immunoreactivity in response to decreased dopamine neurotransmission have been identified. It will be determined if the synaptic relationships of the intrastriatal axons of these subpopulations are different. Finally, a third experiment with possible functional significance is proposed. Specifically, it will be determined whether one of the neurotensin-accumulating subpopulations, i.e., the one that exhibits neurotensin immunoreactivity following 6- hydroxydopamine lesions, gives rise to local axons that preferentially contact stratonigral neurons that become supersensitive to dopamine D-1 receptor agonists following the same lesions. These experiments will contribute to an understanding of how dopamine influences systems that traverse the striatum, which is essential to understanding the role of the striatum in motor control and reward mechanisms, how these functions are linked in the forebrain circuitry, and why therapeutic, motor, psychomotor and addictive implications accompany drugs that replace dopamine, enhance its release or inhibit its uptake.
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