Diagnosis of hearing disorders of central origin is in a primitive state, largely because our understanding of the auditory system decreases markedly as one moves centrally from the cochlea. Probably many subtle central auditory disorders have yet to even be described. Foundational for understanding the function of any part of the brain is knowledge of its chemistry. Both medical and illicit use of drugs have demonstrated that chemical imbalances can dramatically affect behavior of all types. Chemical imbalances in the central auditory pathways would be expected to result in faulty processes of information about the sound environment, and might manifest themselves, not as loss of hearing, but as distorted hearing, including perception of sounds not actually present (e.g., tinnitus or hallucinations) or misinterpretation of environmental sounds. Since the auditory system is so fundamental to human communication, it may not be too far-fetched to suggest that some individuals classified as mentally disturbed may be suffering from a chemical disorder of the central auditory system. Many chemical imbalances that affect behavior involve communication between neurons, which has been found to involve chemical transmitters at virtually all synaptic junctions in mammals. 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. Neurotransmitter chemistry will be emphasized, especially that of acetylcholine, which has been well-established for many years at autonomic and neuromuscular synapses, and the amino acids aspartate, glutamate, glycine and gamma-aminobutyrate, which may be the most prominent transmitter in the brain. In order to reach a functional appreciation for the chemistry, close correlations with anatomical and physiological findings are necessary. In the proposed work, quantitative histochemistry, involving chemical determinations for microscopic pieces of tissue, and high-resolution immunohistochemistry will be combines with tract-tracing anatomy to provide insights about the magnitudes, sources and terminations of cholinergic and amino acid pathways related to the cochlear nucleus. Effects of acetylcholine and amino acid transmitters and related drugs on cochlear nucleus neurons will be studied using an in vitro slice preparation. The microchemistry of the slices will begin to be evaluated, especially for amino acids. Release of amino acids from the slices and their quantitative distributions within the slices will be measured.
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