Clinical abnormalities such as receptive aphasia, auditory perceptual dysfunction and neural presbycusis may involve neurochemical fault(s) of the central auditory pathway. Understanding the neurochemical basis of sensory processing in these structures could lead to development of agents to treat these clinical conditions. The superior olivary complex (SOC) and cochlear nucleus (CN) are important structures in processing acoustic information. The proposed studies will continue to identify, characterize and evaluate the role of putative neurotransmitters in these auditory structures. Studies in the chinchilla CN and SOC are designed to examine the role of inhibitory and excitatory amino acid neurotransmitters in the coding process. Extracellular iontophoretic studies will be used to examine the role of GABA and glycine in the coding of specific inhibitory responses seen for dorsal cochlear nucleus (DCN) neurons. The glycine antagonist, strychnine, has been shown to block suppression seen as nonmonotonic rate-intensity functions for certain DCN neurons. The role of excitatory neurotransmitters in the generation of specific response patterns in the medial nucleus of the trapezoid body (MNTB) and the lateral superior olivary (LSO) nucleus will also be examined. Previous iontophoretic studies in this laboratory have examined the principal neurons of the LSO which display inhibition upon binaural stimulation. Glycine has been implicated as an inhibitory neurotransmitter released by neurons projecting from the MNTB onto LSO neurons. Preliminary intracellular data suggest that inhibitory postsynaptic potential (IPSP) evoked by contralateral stimulation subserves binaural inhibition in the LSO. Attempts will be made to characterize the amplitude, duration and reversal potential of this IPSP. Iontophoretic application of glycine and its receptor antagonist, strychnine, will enable tests of mimicry (identity of action) and antagonism (pharmacologic identity) of the synaptically-released neurotransmitter mediating the contralaterally-evoked IPSP. Later studies will characterize the ipsilaterally-evoked EPSP also observed in our preliminary studies. In conjunction with these experiments, intracellular record-marking studies using horseradish peroxidase (HRP) will allow us to better establish a structure-function correlation for the principal neurons of the LSO. Results from these studies should lead to a better understanding of the role of neurotransmitters in processing the acoustic message in normal adult animals and lead to future studies on potentially neurotransmitter-based acoustic disorders.
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