Multichannel optogenetic stimulation of the auditory pathway using microfabricated LED cochlear implants in rodents

Abstract

When hearing fails, electrical cochlear implants (eCIs) provide the brain with auditory information. One important bottleneck of CIs is the poor spectral selectivity that results from the wide current spread from each of the electrode contacts. Optical CIs (oCIs) promise to make better use of the tonotopic order of spiral ganglion neurons (SGNs) inside the cochlea by spatially confined stimulation. Here, we established multichannel oCIs based on light-emitting diode (LED) arrays and used them for optical stimulation of channelrhodopsin (ChR)−expressing SGNs in rodents. Power-efficient blue LED chips were integrated onto microfabricated 15-μm-thin polyimide-based carriers comprising interconnecting lines to address individual LEDs by a stationary or mobile driver circuitry. We extensively characterized the optoelectronic, thermal, and mechanical properties of the oCIs and demonstrated stability over weeks in vitro. We then implanted the oCIs into ChR-expressing rats and gerbils, and characterized multichannel optogenetic SGN stimulation by electrophysiological and behavioral experiments. Improved spectral selectivity was directly demonstrated by recordings from the auditory midbrain. Long-term experiments in deafened ChR-expressing rats and in nontreated control animals demonstrated specificity of optogenetic stimulation. Behavioral studies on animals carrying a wireless oCI sound processor revealed auditory percepts. This study demonstrates hearing restoration with improved spectral selectivity by an LED-based multichannel oCI system.

Developing Fast, Red-Light Optogenetic Stimulation of Spiral Ganglion Neurons for Future Optical Cochlear Implants

“…Photosensitization of neurons can be achieved by optogenetics, i.e., expressing Channelrhodopsins (ChRs) in the plasma membrane of neurons (Nagel et al, 2003;Boyden et al, 2005). Optogenetic stimulation of the SGNs was shown to activate the auditory pathway (Hernandez et al, 2014;Duarte et al, 2018;Keppeler et al, 2018;Mager et al, 2018;Wrobel et al, 2018;Dieter et al, 2019Dieter et al, , 2020bKeppeler et al, 2020;Thompson et al, 2020) and to restore hearing in various models of deafness (Hernandez et al, 2014;Mager et al, 2018;Wrobel et al, 2018;Keppeler et al, 2020). Recent studies, characterizing the cochlear spread of excitation by recordings from the inferior colliculus, validate the advantage of optogenetic SGN stimulation over conventional electrical stimulation (Dieter et al, 2019(Dieter et al, , 2020bKeppeler et al, 2020).…”

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

“…Multichannel oCI and eCI probes were designed to fit the dimensions of the scala tympani of the rat cochlea (length of 7 ∼ mm, ref. 81) and have been described in previous studies: eCI 82 and oCI 36 . They will be briefly introduced.…”

“…After proving that the sound processor can be triggered by acoustic clicks to elicit light stimulation which retrieves pre-trained avoidance behaviour 36 , we moved to the first in vivo application of the sound processor using coding strategies. Beforehand we had identified that operating all LEDs at 30 % intensity still was sufficient to trigger behavioural response, pointing towards TL below that value.…”

Multichannel optogenetics combined with laminar recordings for ultra-controlled neuronal interrogation

“…an optical ber surrounded by tetrodes 2 . This has been re ned with a single-tip approach 3 , integrated bers in electrode arrays 4 as well as using micro light -emitting diodes (µ-LEDs) combined with recording probes or co-integrated in silicon-based probes [5][6][7][8] . Here we focused on the optimization of optical bers as they allow targeting single cells as well as well as covering large volumes while keeping the exibility to apply any desired wavelength via an external exchangeable light source.…”