A primary function of the auditory system is the localization of sound sources. To accomplish this task the auditory system uses several cues, most notably binaural intensity and timing differences. The system's ability to process timing information rests largely on its capacity to respond to acoustic stimulation in a phase-locked fashion. This ability, which extends to frequencies near 10 kHz, imposes extraordinary demands on the synapses that relay auditory information, and particularly on those linking hair cells to afferent nerve fibers. How the auditory system accomplishes this feat, however, remains largely a mystery. The long term objective of this proposal is to elucidate the mechanisms that allow hair cell synapses in the auditory system to so precisely relay timing and intensity information. The objectives of this proposes are twofold: first, it is essential to characterize how transmitter release varies in hair cells as a function of the frequency and intensity of stimulation. This goal will be accomplished through the use of detached patches of neuronal membrane, which will be used to detect excitatory amino acids, the class of neurotransmitter employed by hair cells. Second, to explain the range of frequencies and intensities within which hair cells synapses can operate effectively it is necessary to gain a better understanding of the key elements of the afferent synapse. This goal includes the characterization of the temporal and spatial variations in the intracellular concentration of Ca2+ in the vicinity of release sites, as a function of the frequency and intensity of stimulation. The activity of Ca2+ near synaptic sites will be studied using Ca2+ sensitive fluorescent dyes as well as the hair cell's own Ca2+ activated potassium channels. A precise understanding of how timing and intensity signals are related should provide a clearer picture of how the auditory periphery processes acoustic information. In addition, a better understanding of synaptic function in the auditory system could improve not only our understanding of sound localization but of audition in general. It is hoped that such an understanding would lead to improved treatments for the hearing impaired and for the design of aids to alleviate this impairment.
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