The formation of chemically-mediated inhibitory synapses is a requisite step in the cascade of events which lead to the maturation of the nervous system and its underlying integrative capacity. Although the consequences of immature inhibitory mechanisms on neural encoding may be substantial at the level of the inferior colliculus (IC), very little is known regarding the developmental processes underlying the maturation of inhibitory neuronal circuits within this structure. The proposed study will be the first of a series of experiments, the long-range purpose of which is to examine changes in synaptic function during development and, in particular, to determine how the acquisition of inhibitory synapses is involved in the maturation of neuronal function within the interior colliculus. The inhibitory synapses targeted in the proposed study will be those mediated by gamma-aminobutyric acid (GABA) and glycine, because substantial evidence from the adult suggests that these amino acids fulfill neurotransmitter roles within the IC. The hypotheses to be tested are: (1) that the inferior colliculus undergoes significant alteration regionally in the appearance and expression of the putative inhibitory neurotransmitters, GABA and glycine, during development, and (2) that changes occur in the physiological and pharmacological attributes of GABAergic and glycinergic synapses within different regions of the IC during development. The development of GABA-ergic and glycinergic synaptic transmission will be studied by (1) mapping the location and time course of changes in GABA and glycine immunoreactive neurons and terminal profiles (puncta) within the IC during postnatal development using standard immunocytochemical techniques, and (2) recording responses of single neurons located in different regions of the IC to acoustic stimulation in the presence and absence of GABAergic and glycinergic agonists and glycinergic responses during development. The latter will be accomplished using standard electrophysiological recording techniques combined with microionophoresis of the neuroactive agents. In addition to furthering our understanding of certain aspects of the biological basis for auditory system development, the proposed study may have important implications in our understanding and treatment of clinical disorders which affect the human infant during development. Many hazardous environmental agents may affect inhibitory synapses, and congenital anomalies may alter or be the result of abnormalities in neurotransmission, producing neurotransmitter deficits, excesses or imbalances. Thus, understanding the fundamental neurochemical properties of the developing auditory system is an important prerequisite to the identification of treatments designed to correct or reduce the effects of congenital auditory dysfunction.

National Institute of Health (NIH)
National Institute on Deafness and Other Communication Disorders (NIDCD)
Small Research Grants (R03)
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Special Emphasis Panel (SRC (03))
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