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GABA, substance P and the efferents of the striatum Vincent, Steven Robert


The efferent pathways from the striatum to the other nuclei of the basal ganglia were examined biochemically and histochemically. Acetylcholine, GABA, enkephalin and substance P have all been suggested to occur in striatal neurons, and markers for these possible transmitters were therefore measured in various nuclei of the basal ganglia following knife cuts of the striatal efferent fibres. These studies confirmed the existence of GABA projections from the head of the striatum to the globus pallidus (GP), entopeduncular nucleus (EP) and substantia nigra (SN). In addition the presence of substance P in the striatal projection to the EP was demonstrated and the substance P projection to the SN was confirmed using a radioimmunoassay. The first evidence suggesting the presence of both substance P and methionine-enkephalin in the striatopallidal fibres was also obtained. Also the important observation that methionine-enkephalin is not present in the projections from the head of the striatum to the EP and SN was noted. In order to visualize substance P fibres in the brain a new method for immunohistochemical studies of the nervous system was developed based on the biotin-avidin system. Using this powerful technique substance P fibres and terminals were observed in the striatum, GP, EP and SN, as well as in various other areas including the amygdaloid complex, the habenula and the interpeduncular nucleus. This represents the first report of substance P fibres in the basal ganglia demonstrated using an immunoperoxidase procedure. The enzyme GABA-transaminase (GABA-T) was examined as a potential marker for the GABA neurons of the basal ganglia. Using selective lesions and a biochemical assay procedure the enzyme was found to be present in the neurons of the striatum and in the striatonigral pathway. GABA-T was apparently not present in the glial elements of the striatum nor was it present in the nigrostriatal dopamine neurons. Histochemical experiments demonstrated GABA-T to be present in the terminals of the striatal and pallidal efferents which are thought to use GABA as a transmitter. These experiments establish the usefulness of GABA-T histochemistry as a new method for the analysis of the topography of the GABA systems in the basal ganglia. The response of the GABA and substance P cells in the basal ganglia to the selective removal of the dopamine cells of the SN was examined and compared with the pathological findings observed in Parkinson's disease. In contrast with the decrease reported in glutamate decarboxylase activity in the basal ganglia in Parkinson's disease, an increase in the activity of this enzyme was observed in the animal model. Also, a significant decrease in nigral and striatal substance P levels occurred following this lesion. The implications of these findings for the etiology and pharmacological therapy of Parkinsonism are discussed. Finally, the nigrotectal pathway was examined ultrastructurally and biochemically since it represents a major output pathway of the basal ganglia. A selective decrease was found in the glutamate decarboxylase activity of the superior colliculus following lesions of the SN. This observation provides the first indication that the nigrotectal projection may use GABA as a transmitter. Electron microscopic examination of axon terminals of the nigrotectal pathway indicated the axons were probably myelinated and that the terminals form symmetric synapses with the major dendrites of neurons in the deep layers of the superior colliculus.

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