Timing is of central importance in hearing - this principle is reflected in the greater temporal precision of stimulus locked responses in neural circuits responsible for auditory processing as compared with visual processing. However, beginning with the auditory thalamus and continuing to cortex, neurons exhibit spiking patterns that are no longer phase-locked to stimulus features. The mechanisms by which the thalamic circuit transforms a stimulus-locked code into another, as-of-yet undefined code are thus intimately related to the precise temporal filtering operations that are implemented. This proposal seeks to elucidate those mechanisms with a new precision using a new information-theoretic method for deriving those temporal filtering operations from recorded spike trains in concert with slice electrophysiology and light-activated ion channels targeted to specific cell types. This work may have relevance to the development of auditory prostheses - in the same way that early cochlear implants did not take advantage of the tonotopic mapping of the auditory nerve, future generations of auditory implants may use knowledge about the temporal transformation of inputs that occurs in the brainstem and thalamus. Understanding the profound transformation of afferent information that occurs in the thalamus may bridge the gap between what is known about brainstem encoding of auditory information and what is not known about higher-level representations of auditory stimuli in the cortex. Optical control of collicular inputs to the medial geniculate nucleus may also represent an alternative method for auditory prosthetic devices.

Public Health Relevance

The success of cochlear implants for treating deafness has been remarkable - yet this technology is ultimately fruitless for patients with lesions beyond the cochlea, so auditory brainstem implants have been in development since the 1970s to directly stimulate the next level of auditory processing. This proposal seeks to decipher the nature of the encoding of timing information in the auditory thalamus using a combination of advanced biophysical and computational techniques, so that future generations of auditory implants can benefit from this improved knowledge. The project also represents an application of optical control of neural activity in the auditory system, a potentially exciting avenue for future prosthetics research.

National Institute of Health (NIH)
National Institute on Deafness and Other Communication Disorders (NIDCD)
Individual Predoctoral NRSA for M.D./Ph.D. Fellowships (ADAMHA) (F30)
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Communication Disorders Review Committee (CDRC)
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Sklare, Dan
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Salk Institute for Biological Studies
La Jolla
United States
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