Optogenetic Stimulation in a Model of the Auditory Brainstem Implant

Harvard Medical School, Boston MA

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Abstract

? DESCRIPTION (provided by applicant): The auditory brainstem implant (ABI) is a neuroprosthesis that restores hearing sensations for deaf people who cannot benefit from a cochlear implant (CI). This implantable device exists of a paddle-style electrode array with electrode contacts along its surface and is placed on the smooth cochlear nucleus (CN) surface of the auditory brainstem. Individual electrodes stimulate the CN to provide frequency/spectral cues and temporal cues to convey multiple features of speech. ABI users typically have speech comprehension performance that is poorer than normal hearing individuals and poorer than users of the cochlear implant, another auditory prosthesis that stimulates the nerve fibers of the cochlea. Two types of information provided in limited degrees by the ABI that are correlated with hearing outcomes are spectral cues and temporal cues. Furthermore, the ABI has the added challenge of delivering these cues to the CN, which contains a number of excitatory and inhibitory neurons that are stimulated indiscriminately by the device. To address the limited success of electrical stimulation in the ABI, we propose an alternative mode of stimulation, one that was recently discovered (Boyden 2005) and is now being used by neuroscientists around the world: optogenetics. Compared to electrical stimulation, optogenetic stimulation uses light to stimulate neurons that have been specifically targeted via gene transfer. As light may be more focused than electrical stimulation, optogenetic stimulation may improve spectral and temporal cues. Additionally, as sensitivity to light may be specifically targeted in a select group of cell types, optogenetic stimulation provides a clear means for dealing with the cellular complexity of stimulated tissue in an ABI model. In this proposed project, we apply optogenetic stimulation in a model for ABI that we have recently established in the mouse. Using acute experiments that record the evoked neural activity, we will determine whether optogenetics improves spectral and temporal cues (Aim 1), and provides a means to bypass the cellular complexity of the CN (Aim 2). Furthermore, since ultimately we want to test whether optogenetic stimulation can provide the same or better information than electrical stimulation, we will compare optogenetic stimulation with electrical and the acoustic stimulation used in natural hearing. While acute studies can address fundamental questions of neurostimulation, it remains elusive whether specific patterns of evoked neural activity translate to perceptual advantages. We will apply the studies of Aims 1 and 2 to direct a behavior experiment measuring the perceptual saliency of optical stimulation (Aim 3). These experiments will determine whether mice are able to hear different stimulations provided by optical stimulation and to compare that with perceptions provided by electrical or acoustic stimulation.