Although common anatomical and neurochemical features characterize all of ventral and dorsal striatum, if function is considered, it is inescapable that profound differerences must accompany the similarities. Accordingly, an investigation of substrates that reflect anatomical dissociation of ventral from dorsal striatum is proposed, Based upon sample preliminary results, which are related in the body of the grant proposal, it is suggested that peptide expression in striatal neurons is tonically enabled or facilitated by one component of the mesostriatal projection and inhibited by another. The interplay between the opposing dopamine systems, moreover, is postulated to differ in ventral an dorsal striatum and, perturbed, to result in more or less transient changes in the striatal peptidergic milieu which are transmitted to basal ganglia effector structures via stristifugal projections. Perikaryal neurotensin expression is very sensitive to dopaiminergic perturbation, more easily elicited in striatal matrix than patches and more conspicuous ventrally than dorsally, and so can be utilized as a discrete, experimentally advantageous indicator of peptide expression. In addition we have tentatively identified imorphological substrates of the postulated opposing dopaminergic inputs. Consequently, testable hypotheses are stated. Hypothesis I The capacity of striatal neurons to express neurotensin immunoreactivity should be be reflected in their synaptic inputs. The presence or absence of perikaryal neurotensin immunoreactivity in various pharmacologic or neurotoxic circumstances will be related quantitatively to synaptic organization reflective of opposing axodendritic dopaminergic inputs. Hypothesis Il - changes in patterns of striatal peptide expression are conducted along striatifugal pathways and result in redistributions of neuromodulatory influences in effector regions of the basal ganglia. The topography and chemospecificity of striatifugal pathways that originate parts of striatum where enhanced neurotensin expression can be elicited will be demonstrated and the ultrastructural relationships of their axon terminals with postsynaptic neurons described. The results of these studies will provide anatomical data essential the interpretation of functional studies dissociating ventral and dorsal striatal mechanisms, particularly those suggesting that peptidergic neurotransmission underlies some behavioral sequelae associated with dopaminergic perturbation. In concert, the two components of the proposed investigation should contribute to bridging conceptual gaps separating structure and function in striatum.
Showing the most recent 10 out of 72 publications
