Hearing the Light: A Behavioral and Neurophysiological Comparison of Two Optogenetic Strategies for Direct Excitation of Central Auditory Pathways
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CitationChen, Jenny X. 2016. Hearing the Light: A Behavioral and Neurophysiological Comparison of Two Optogenetic Strategies for Direct Excitation of Central Auditory Pathways. Doctoral dissertation, Harvard Medical School.
AbstractFor deaf individuals with absent/damaged cochleae or auditory nerves, the auditory brainstem implant (ABI) is the only option to restore hearing. However, most ABI users have only sound awareness without meaningful speech comprehension. These electrical implants are limited by crosstalk between neighboring electrodes that indiscriminately activates large groups of neurons. In contrast, optogenetics provides a means to manipulate neural circuits with temporal and spatial precision by using light to activate genetically modified neurons expressing light-gated ion channels called channelrhodopsins. However, central auditory neurons fire at speeds that exceed the limits of most available channelrhodopsins. In this study, we explored the feasibility of an optogenetic auditory prosthesis by infecting neurons of the murine inferior colliculus (ICc) with viruses expressing standard channelrhodopsin-2 (ChR2) and Chronos, a newly discovered opsin with ultra-fast channel kinetics.
Through extracellular in vivo recordings in the ICc, we found that while ChR2-driven neurons can synchronize stimulation rates up to nearly 80 Hz, neurons infected with Chronos entrained pulses as fast as 200 Hz, approximating the synchronization limit for natural acoustic input in the midbrain. Optical stimulation of Chronos at rates as high as 300 Hz evoked minimally-adapting responses, although spikes were no longer fully synchronized. Chronos mediated responses support a superior code for the detection and discrimination of high pulse rates as compared with ChR2.
It was hypothesized that this improved temporal fidelity might translate into better behavioral detection of optogenetic stimulation. After unilateral ICc injections of saline or viral constructs, mice were trained to perform an auditory avoidance task. An optic fiber assembly was implanted into the injected ICc and the detection task was repeated with photostimulation in the place of acoustic input. Chronos and ChR2 expressing mice exhibited similar detection slopes, while saline injected animals performed at chance.
These findings suggest that while Chronos can transform a range of stimulation patterns with higher accuracy compared with ChR2, this does not translate into a perceptual advantage. This project has implications for both the future design of auditory prostheses and our understanding of signal processing in central auditory pathways.
Citable link to this pagehttp://nrs.harvard.edu/urn-3:HUL.InstRepos:27007736