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. Only a few of the neurotransmitter substances are fairly well established, including acetylcholine, several catecholamines and serotonin, several amino acids, and some peptides. As would be expected, imbalances in any of these neurotransmitter systems 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 synaptic chemistry of the cochlear nucleus, the first brain center of the auditory system. It is intended to obtain chemical data at such a resolution as to readily permit correlations with the considerable anatomical and physiological data available for the cochlear nucleus. This can be done via the methods of quantitative histochemistry, by which quantiatative chemical data can be obtained for pieces of tissue as small as 20 Mum in linear dimension. The locations of these tissue samples can be 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 related to the cochlear nucleus, but have also raised new questions. These will be addressed especially by further measurements of the activity of choline acetyltransferase (the enzyme of synthesis for acetylcholine) in the cochlear nucleus and some closely related structures - the cochlea and the superior olivary complex. The scope of the project will also be expanded to include some of the proposed amino acid neurotransmitters (especially Gamma-aminobutyric acid, glycine, glutamate and aspartate, which have all been implicated in cochlear nucleus function) and related enzymes (aspartate aminotransferase, glutaminase and glutamic acid decarboxylase). These will be measured in the same sets of sections of lesioned animals as used for measurements on the cholinergic system and the distributions compared to those of control animals.
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