ONTOGENY OF COCHLEAR NUCLEUS RESPONSES TO AMINO ACIDS

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Response properties of developing auditory neurons suggest that synaptic function may be immature during early postnatal development. Response latencies are prolonged, temporal discharge patterns do not display the characteristic adult-like patterns, dynamic ranges of input/output functions are greatly reduced, and discharge synchronization (i.e., phase-locking) is diminished. To determine the contribution that immature synapses make to these developing response patterns, we propose to study the electrophysiological and pharmacological development of neurons within the dorsal (DCN) and posteroventral (PVCN) cochlear nuclei (CN) of kittens. The overall hypothesis to be tested is that immature response properties of DCN and PVCN neurons recorded from young animals are the result of immature synaptic mechanisms. Synaptic transmission will be assessed electrophysiologically by examining neuronal responses to acoustic stimulation throughout postnatal development. We will evaluate postsynaptic receptor function prior to the age at which acoustically-evoked responses are elicited (e.g., between birth and 5-7 postnatal days), by examining the effects of excitatory (glutamate and aspartate) and inhibitory (gamma-aminobutyric acid (GABA) and glycine) amino acids microiontophoretically applied onto DCN and PVCN neurons. Receptor specificity of amino acid-mediated excitation or inhibition will be evaluated by the simultaneous administration of specific receptor antagonists during amino acid application and during acoustic stimulation. Throughout development, we will determine the effects of the putative amino acid neurotransmitters and their antagonists on discharge rate, discharge synchronization, response thresholds, the frequency limits of responsiveness, and on temporal discharge patterns throughout the response area of CN neurons. Finally, we hypothesize that the time course of receptor activation (i.e., time to maximum effect) following amino acid administration, and the time course over which discharge activity is terminated after cessation of microiontophoresis, varies during postnatal development, and that the characterization of that process can be used to map the maturation of synaptic transmission within the CN. These studies represent an initial investigation of developmental aspects of chemical neurotransmission in the auditory system, which is an important first step in the development of therapeutic, pharmacologic strategies aimed at the treatment of hearing anomalies that may be characterized by neurochemical imbalance.