The proposed studies will elucidate two aspects of neuropeptide localization in the amniote brain: 1) the relationship of the neuropeptidergic projection circuits of the basal ganglia to one another, and 2) the extent and significance of co-localization for two specific pairs of peptides. These studies will be carried out in birds and reptiles because their brains are fundamentally similar in organization to those of mammals, but simpler, and may therefore provide valuable model systems for study. Studies on peptidergic projection circuits of the basal ganglia will help determine the respective roles of the different striatal transmitters and modulators. LM and EM immunohistochemical techniques and pathway tracing techniques will be used to study: 1) the strionigral projection systems that contain substance P (SP), dynorphin and GABA, and 2) the striopallidal projection systems that contain SP, dynorphin and enkephalin. For both systems, the neurons containing each transmitter or peptide will be localized and their relative numbers ascertained. In addition, the location of the different populations of strionigral projection neurons will be determined with respect to the location of the striopallidal projection neurons. The possibility that two or three of the above substances are contained in the same neurons will be examined. These studies will help clarify the nature of the transmitter deficits in degenerative striatal disorders such as Huntington's disease. Other studies on the avian basal ganglia will determine whether tectal neurons receiving enkephalinergic pretectally-relayed input from the pallidum project to brainstem """"""""premotor"""""""" cell groups and will also determine the opioid peptide receptor type involved in the enkephalinergic pretectal-tectal synapses. Studies on the linkage of the basal ganglia into the motor system may help clarify the mechanisms by which the basal ganglia affect motor functions. Studies on peptide-peptide co-localization will determine the distribution in the avian and reptilian brain of neurons an terminals containing either SP and enkephalin or SP and cholecystokinin-8, using and LM immunohistochemical double-label procedure. The potential widespread co-occurrence of these common peptides in brain may have great implications for our understanding of their role in the regions where they co-occur. Finally, double-label EM immunohistochemical techniques will be used in one system to determine whether SP and enkephalin are present in the same synaptic vesicles. Such information will help clarify the functional roles of these co-existent peptides.
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