The long term goal is to investigate the distribution of putative cerebellar neurotransmitters in the deep cerebellar nuclei and to analyze the possible relationship of the inhibitory transmitter GABA and the putative excitatory transmitters glutamate and aspartate with major cerebellar efferent projections. 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 in this region is unknown. Since knowledge of neurotransmitter localization in the deep nuclei is lacking, the present proposal is designed to provide data related to the distribution of putative cerebellar transmitters among the cerebellar nuclei. The proposed experiments will provide basic anatomical and biochemical information relevant to our understanding 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 plot the location of serotonin-like immunoreactive axons in the cerebellar nuclei and to determine the specific origin of these axons. 2. To analyze the specific distribution and determine the brain stem origin of corticotrophin releasing factor-like immunoreactive axons among the cerebellar deep nuclei. 3. To study the location and distribution of the putative excitatory neurotransmitters glutamate and aspartate in both the cerebellar deep nuclei and cortex. 4. To determine if the cerebellorubral, cerebellothalamic and cerebello-olivary projections contain glutamate, aspartate, pipecolic acid or GABA. The results obtained will provide important data on both the distribution and origin of axons containing specific, putative neurotransmitter substances in the deep cerebellar nuclei. In addition novel data will be obtained regarding the relationship of excitatory amino acid transmitters to the cerebellar nuclei and to cerebellar efferent projections.
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