Neural mechanisms of sound intensity coding

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Project Summary. A detailed understanding of the neurophysiological basis of hearing is fundamental to the understanding of human hearing impairment and the guidance of further development of the most successful prosthetic intervention to date, the cochlear implant. Yet we still lack a complete description of how sound information is processed at even the first central nervous system relay, the cochlear nucleus. Our experiments in the avian model system focus on the first central nervous system target of the auditory nerve, the cochlear nucleus angularis, which initiates the ascending pathways involved in localization using binaural sound level cues and spectrotemporal processing. Rapid adaptation is crucial for neural coding of complex sounds and scenes by implementing temporal filtering, dynamic range adaptation and generating noise-invariant signal representations. Dynamic range adaptation occurs when auditory neurons adjust their firing rate-level encoding depending on the statistics of the acoustic stimulation, shifting upward with louder sound distributions. Adaptive cellular processes such as short-term synaptic plasticity (activity-dependent alterations in synaptic weight), intrinsic firing rate adaptation (via ion channel inactivation or hyperpolarizing currents), and modulatory transmitter feedback via second messenger systems are all candidate mechanism for implementing intensity-related adaptation. Using a combination of in vitro physiology, modeling and in vivo recordings, we will investigate an intrinsic mechanism called threshold adaptation and its reliance on the inactivation of sodium channels. We also test the hypothesis that short-term synaptic plasticity contributes to solving the `dynamic range problem': how human can hear across many orders of intensity magnitude in behavioral experiments given the (formerly known) limited physiological range of nerve fibers. Given the recent advances in the restoration of hearing using prosthetic devices that stimulate the auditory nerve, it is critical to understand how nerve activity is interpreted by the central nervous system. This research will provide new data on how acoustic information is transmitted from the auditory nerve to the first central relay in normal hearing, and thus can provide a reference for devices such as cochlear implants that stimulate the nerve directly. The emphasis on temporal envelope coding may also provide new information on disorders that may be related to disrupted temporal processing, such as age-related hearing loss or auditory neuropathy, which can lead to a common but disabling difficulty with understanding speech in noise.