Vavakou, A. | bioRxiv Science

bioRxiv2026

Multichannel optical cochlear implants enable spectrally distinct auditory activity

When hearing fails, cochlear implants (CIs) restore auditory perception. Yet, coding of spectral information remains a bottleneck because each electrode broadly activates the auditory nerve. As light can be more conveniently confined, optical (o)CIs present an alternative. Here, we combined expression of the potent channelrhodopsin ChReef in spiral ganglion neurons (SGNs) with oCIs comprising 5-10 green LEDs in gerbils. This combination enabled systematic comparison of encoding intensity and spectral information by individual oCI channels to acoustic and electrical stimulation within a translationally feasible energy range. Recordings from the inferior colliculus (ICC) showed that ChReef aligned SGN light sensitivity with LED radiant fluxes: ICC activity had thresholds <200 nJ and reached a maximum equivalent to that achieved with 51 dB SPL pure tones. Multichannel oCIs enabled tonotopically ordered, spectrally distinct stimulation that more closely resembled acoustic stimulation than did electrical stimulation. Some LEDs elicited multiple spectral peaks at higher intensities. Linear discriminant analysis of ICC activity indicated improved channel discriminability for optical over electrical stimulation. In summary, ,micro-joule oCI-stimulation achieves improved spectral resolution over state-of-the-art electrical stimulation.

neuroscience↗

bioRxiv2026

Optogenetic cochlear stimulation evokes midbrain activity with near-physiological temporal fidelity

When hearing fails, stimulation of the auditory nerve by electrical cochlear implants (eCIs) partially restores hearing, with most eCI users achieving open speech understanding. However, the broad current spread from each electrode limits frequency coding and speech understanding in daily situations with background noise. Spatially confined optogenetic stimulation by future optical cochlear implants (oCIs) improves frequency coding but millisecond closing kinetics of channelrhodopsins (ChRs) might limit temporal coding. Here, we evaluated the utility of fast-closing f-Chrimson for processing temporal information in the auditory system of Mongolian gerbils. We recorded neural activity in the inferior colliculus evoked by f-Chrimson-mediated optogenetic stimulation of the cochlea. F-Chrimson enabled energy-efficient stimulation of the auditory pathway at rates [≥]150 Hz, outperforming the slower ChR variants CatCh (blue) and ChReef (green). Energy thresholds for activation of the auditory pathway were in the low {micro}J range, between ChReef (sub-{micro}J) and CatCh. Dynamic range and frequency selectivity were comparable to previous observations with CatCh and outperformed electrical stimulation. In conclusion, employing fast-gating ChRs harnesses improved spectral coding without degrading temporal coding. The Paper Explained ProblemElectrical cochlear implants (eCIs) partially restore speech comprehension in most of 1 million otherwise severely deaf people. However, most CI-users face challenges hearing in daily situations. Spectrally more selective stimulation of the auditory nerve by optical cochlear implants (oCIs) promises to overcome this limitation. However, the closing kinetics of channelrhodopsins (ChR) limit the temporal bandwidth of bionic sound coding. Improving the ChR properties and evaluating temporal coding remain major objectives for developing hearing restoration by oCI. ResultsHere, we evaluate the utility of waveguide-based oCI using the fast-closing ChR Chrimson (f-Chrimson) for encoding of temporal, spectral and intensity information by multi-electrode-array (MEA) recordings from the midbrain. We compare f-Chrimson-mediated bionic coding to acoustic coding as well as to previous data acquired with optogenetic stimulation using other ChRs and with electrical stimulation. F-Chrimson enabled energy-efficient stimulation of the auditory pathway at rates [≥]150 Hz, outperforming the slower ChR variants CatCh (blue) and ChReef (green). Intensity and frequency coding were comparable to previous observations with CatCh and outperformed electrical stimulation. ImpactThis study demonstrates near physiological temporal coding with the fast-closing ChR f-Chrimson, indicating that improved spectral coding by oCI is not traded off by poor temporal fidelity.

neuroscience↗

bioRxiv2023

Efficient and sustained optogenetic control of nervous and cardiac systems

Optogenetic control is used to manipulate the activity of specific cell types in vivo for a variety of biological and clinical applications. Here we report ChReef, an improved variant of the channelrhodopsin ChRmine. ChReef offers minimal photocurrent desensitization, a unitary conductance of 80 fS and closing kinetics of 30 ms, which together enable reliable optogenetic control of cells at low light levels with good temporal fidelity and sustained stimulation. We demonstrate efficient and reliable red-light pacing and depolarization-block of ChReef-expressing cardiomyocyte clusters. We used AAV-based gene transfer to express ChReef in retinal ganglion cells, where it restores visual function in blind mice with light sources as weak as an iPad screen. Toward optogenetic hearing restoration, ChReef enables stimulation of the auditory pathway in rodents and non-human primates with nano-Joule threshold, enabling efficient and frequency-specific stimulation by LED-based optical cochlear implants.

biophysics↗