The long term goal of this research is to investigate the distribution of putative cerebellar neurotransmitters and their receptors in the deep cerebellar nuclei and to analyze the relationship of the cerebellar nuclei with brain stem monomaine systems. In view of the fact that the cerebellar cortex can exercise its influence on the rest of the brain only through its projection upon the central nuclei, it is extraordinary how little attention has been paid to the deep cerebellar nuclei until recently. Recent studies of the deep nuclei have indicated that they differ significantly from one another in terms of their functional roles. Whether the functional differences observed among the cerebellar nuclei are due in part to variations in the types or levels of neurotransmitters and their receptors in this region is unknown. Since knowledge of receptor distribution and neurotransmitter localization in the deep nuclei is lacking, the present proposal is designed to provide data related to the distribution of putative cerebellar transmitters and their receptors among the cerebellar nuclei. The proposed experiments will provide basic pharmacological and biochemical information relevant to our standing of the normal function of these subcortical cell groups as well as important avenues for investigation in cases of cerebellar pathology. Our proposed investigation of the deep cerebellar nuclei in this revised proposal is described by the following four specific aims: (1) To analyze and compare the specific distribution of tryptaminergic, serotonergic, and glutamatergic binding sites in the cerebellar nuclei. (2) To plot the location of corticotrophin releasing factor (CRF), pipecolic acid and serotonin-like immunoreactivity in the cerebellar nuclei and to determine the origin of CRF input to the cerebellum. (3) To determine if brain stem monoamine neurons send axon collaterals to multiple deep cerebellar nuclei using retrograde double fluorescent labeling techniques. (4) To utilize a novel technique to analyze specific binding sites on precerebellar neurons, especially monoamine neurons, which project to the cerebellum. The results obtained will provide novel data on both the distribution of putative cerebellar neurotransmitter receptors in the deep cerebellar nuclei and the types of receptors associated with precerebellar neurons. In addition important data will be gained regarding the relationship of monoamine systems to the cerebellar nuclei.
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