The normal function of the nervous system is intimately related to the chemistry of its component parts - the neurons and glia. The communication of coded information between neurons relates to a specific component of this chemistry consisting of neurotransmitter substances and the enzymes associated with their synthesis and degradation. Neurotransmitter chemistry, moreover, is closely interrelated with other aspects of cellular metabolism. Only a few neurotransmitter substances are fairly well established, including acetylcholine, several catecholamines and serotonin, several amino acid and some peptides. As would be expected, imbalances in any of these neurotransmitter system can lead to serious malfunctions in the nervous system, and thus, in sensation, movement or other behavior. To date, very little is known about possible malfunctions of these neurotransmitter systems in hearing disorders. One of the reasons is that so little is known about their roles in normal hearing. This proposal constitutes a step in a long-range effort to understand the chemistry of the cochlear nucleus, the first brain center of the auditory system. In order to reach a functional appreciation for the chemistry, the data are compared with anatomical and physiological information. This is accomplished via the methods of quantitative histochemistry, by which quantitative chemical data can be obtained for pieces of tissue as small as 20 mum in linear dimension. The locations of these tissue samples are recorded to provide a chemical map comparable to anatomical or physiological maps. Previous studies during this project have provided a basic quantitative understanding of the cholinergic (using acetylcholine as transmitter) pathways to the cochlear nucleus. In the next period, autoradiographic methods will be applied to more precisely localize origins and terminations of centrifugal cholinergic pathways to the cochlear nucleus. Additionally, initial data have been obtained for amino acids in pathways connecting to the cochlear nucleus. The present proposal especially focuses on detailed evaluation of the amino acids. Using high performance liquid chromatography (HPLC), concentrations of many amino acids will be measured, including those suggested as neurotransmitters in the cochlear nucleus. Assays of related enzyme activities will be done for amino acids whose concentrations are significantly affected by the lesions. These will be measured in the same sets of sections as used for measurements on the cholinergic system as well as sections of animals with some additional lesions.
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