Optogenetic stimulation of cochlear neurons activates the auditory pathway and restores auditory-driven behavior in deaf adult gerbils

Abstract

Cochlear implants partially restore hearing via direct electrical stimulation of spiral ganglion neurons (SGNs). However, spread of excitation from each electrode limits spectral coding. We explored the use of optogenetics to deliver spatially restricted and cell-specific excitation in the cochlea of adult Mongolian gerbils. Adeno-associated virus carrying the gene encoding the light-sensitive calcium translocating channelrhodopsin (CatCh) was injected into the cochlea of adult gerbils. SGNs in all cochlea turns showed stable and long-lasting CatCh expression, and electrophysiological recording from single SGNs showed that light stimulation up to few hundred Hertz induced neuronal firing. We characterized the light-induced activity in the auditory pathway by electrophysiological and behavioral analysis. Light- and sound-induced auditory brainstem responses showed similar kinetics and amplitude. In normal hearing adult gerbils, optical cochlear implants elicited stable optical auditory brainstem responses over a period of weeks. In normal hearing animals, light stimulation cued avoidance behavior that could be reproduced by subsequent acoustic stimulation, suggesting similar perception of light and acoustic stimuli. Neurons of the primary auditory cortex of normal hearing adult gerbils responded with changes in firing rates with increasing light intensity. In deaf adult gerbils, light stimulation generated auditory responses and cued avoidance behavior indicating partial restoration of auditory function. Our data show that optogenetic cochlear stimulation achieved good temporal fidelity with low light intensities in an adult rodent model, suggesting that optogenetics might be used to develop cochlear implants with improved restorative capabilities.

Ultrafast optogenetic stimulation of the auditory pathway by targeting‐optimized Chronos

“…When increasing stimulus rate, oABR amplitudes declined (Fig G) and latencies prolonged (Fig G and I). However, in contrast to our previous reports on (i) ChR2: where potentials were found only up to 70 Hz (Hernandez et al , ) and (ii) CatCh: up to 200 Hz, and f‐Chrimson: up to 250 Hz (respectively Wrobel et al , ; Mager et al , ), we could detect sizable P 1 ‐N 1 up to stimulus rates of 500 Hz for Chronos (Fig G left, H) and 1,000 Hz for Chronos‐ES/TS (the highest stimulus rate tested in our experiments, Fig G and H). P 1 latency increased with higher stimulus rates in both cases.…”

Hearing restoration by a low-weight power-efficient multichannel optogenetic cochlear implant system

“…This would equate to at least 48 channels for the human cochlea 44 and ∼8-12 for the rat 45 . At the same time, the most efficient pulse duration for optogenetic stimulation which depends on the kinetics of the opsin of choice (0.5-2 ms 24,28,29 ) exceeds that of electrical stimulation (typically below 100 µs 46 ). Moreover, the synchrony of optogenetically driven SGN firing 24,28,29 is lower than that of electrical stimulation [47][48][49] and closer to physiological sound stimulation 24,28,29 .…”

“…The setup was identical as previously used in studies of optogenetic stimulation via optical fibre involving Mongolian gerbils 24 . Briefly, the ShuttleBox is composed of two platforms and a hurdle between them.…”

Optimized Chronos sets the clock for optogenetic hearing restoration

“…Optical CIs have the potential to drastically improve frequency and intensity coding since light can be spatially confined more conveniently. Indeed, recent studies (Hernandez et al , ; Mager et al , ; Wrobel et al , ) have demonstrated improved frequency resolution and larger output dynamic range of cochlear optogenetic stimulation over monopolar electrical stimulation. However, the first study also highlighted a low temporal fidelity of optical stimulation due to the slow closing of channelrhodopsin (ChR) after light off, leading to a breakdown of neural population responses for stimulation above 100 Hz (Hernandez et al , ).…”

“…However, the first study also highlighted a low temporal fidelity of optical stimulation due to the slow closing of channelrhodopsin (ChR) after light off, leading to a breakdown of neural population responses for stimulation above 100 Hz (Hernandez et al , ). Although better temporal coding with selective viral expression of the ChR2‐variant CatCh in SGNs has been reached (Wrobel et al , ), achieving physiological spike rates of several hundreds of Hz and μs spike time precision has remained an important objective.…”