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

Jablonski, Lukasz; Harczos, Tamás; Wolf, Bettina; Hoch, Gerhard; Dieter, Alexander; Hessler, Roland; Ayub, Suleman; Ruther, Patrick; Moser, Tobias

doi:10.1101/2020.05.25.114868

Cited by 5 publications

(6 citation statements)

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“…6). The detailed technological description and characterization are described in a separate manuscript (35). In brief, the oCI sound processor consists of a microelectromechanical systems (MEMS) microphone (Knowles SPH0641LM4H-1) with digital pulse density modulation (PDM) interface, an ARM Cortex M4fbased digital signal controller (DSC) with embedded 2.4-GHz radio module (Nordic Semiconductor nRF52832), an LED driver (Texas Instruments TLC5923), and a battery.…”

Section: Behavioral Analysis Of Optogenetic Activation Of the Auditor...mentioning

confidence: 99%

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

et al. 2020

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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.

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Section: Behavioral Analysis Of Optogenetic Activation Of the Auditor...mentioning

confidence: 99%

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

et al. 2020

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“…Compared with existing wireless multi-channel optogenetic systems, our design presents a smaller LED geometry and a longer communication distance. When more functions or more LED devices are incorporated, the required circuit module will be larger and heavier, and improved circuit design can be utilized to reduce the system dimension ( Jablonski et al., 2021 ). In addition, wireless energy harvesting strategies can be explored to realize battery-free operation, though in this case the communication distance can be limited by the near-field inductive coupling design ( Shin et al., 2017 ; Yang et al., 2021 ).…”

Section: Discussionmentioning

confidence: 99%

A dual-channel optogenetic stimulator selectively modulates distinct defensive behaviors

Xue

Liu

et al. 2022

iScience

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Summary Implantable devices and systems have been emerging as powerful tools for neuroscience research and medical applications. Here we report a wireless, dual-channel optoelectronic system for functional optogenetic interrogation of superior colliculus (SC), a layered structure pertinent to defensive behaviors, in rodents. Specifically, a flexible and injectable probe comprises two thin-film microscale light-emitting diodes (micro-LEDs) at different depths, providing spatially resolved optical illuminations within the tissue. Under remote control, these micro-LEDs interrogate the intermediate layer and the deep layer of the SC (ILSC and DLSC) of the same mice, and deterministically evoke distinct freezing and flight behaviors, respectively. Furthermore, the system allows synchronized optical stimulations in both regions, and we discover that the flight response dominates animals' behaviors in our experiments. In addition, c-Fos immunostaining results further elucidate the functional hierarchy of the SC. These demonstrations provide a viable route to unraveling complex brain structures and functions.

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“…Due to its exceptional physiological relevance, Chronos has a strong stance for future oCI applications. Moreover, blue µLED multichannel implants are already available to elicit reliable physiological and behavioral responses in rodents Jablonski et al, 2020). Therefore, one can test better spatial resolution empowered by experiments using gerbils and rats expressing CatCh, a ChR2 variant, that can generate reliably detectable percepts over months, though not continuously, by blue-light stimulation (Jablonski et al, 2020;.…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

“…Moreover, blue µLED multichannel implants are already available to elicit reliable physiological and behavioral responses in rodents Jablonski et al, 2020). Therefore, one can test better spatial resolution empowered by experiments using gerbils and rats expressing CatCh, a ChR2 variant, that can generate reliably detectable percepts over months, though not continuously, by blue-light stimulation (Jablonski et al, 2020;. Here, durable SGNs are at utmost importance to provide a long-lasting audition through both eCI and prospective medical oCI systems as well.…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

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Optogenetic Manipulation of the Auditory System

Bali¹

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There are millions of people who are affected from sensorineural hearing loss. In this type of deafness, sensory hair cells are typically dysfunctional or lost, and thereby not conveying sound information to brain. The state-of-the-art solution is the cochlear implant (CI) which circumvents the receptor problem via direct electric stimulation of spiral ganglion neurons (SGNs) of that from auditory nerve (AN). Thus, the CI enables hearing and provides open speech comprehension. Yet, for instance in noisy background, in most users, speech comprehension fails likely owing to poor frequency resolution. This results from wide current spread in the the saline-filled cochlea activating large sets of the tonotopically organized SGNs. Here, light can serve as an alternative mode of stimulation since it can be conveniently focused to evoke SGN populations more precisely. Clearly, SGNs are not light sensitive and hence we employ an optogenetic approach. The series of studies presented here gathers under the same roof: How to achieve optogenetic manipulation of the SGNs such that it will suit well to the intrinsic physiological properties of auditory system, be stably maintained for many years, and last but not least be safe? Temporal firing properties of SGNs are uniquely fast allowing fine coding of sound. Therefore, channelrhodopsins (ChRs) used should enable reliable control of light-induced spiking in SGNs. To this end, first, we investigated feasibility of blue-light-gated naturally occurring Chronos with the fastest on-/off-kinetics at the mouse AN with the help of molecular tools, i.e. endoplasmic reticulum exit signal (ES) and membrane trafficking signal (TS), enhancing membrane localization of the ChR. By this way, it was possible to drive the AN up to 1000 Hz stimulation rate. While Chronos suits temporal coding very well, we also sought for red-shifted fast alternatives since chronic exposure to blue light bears risk of phototoxicity in SGNs. Here, the engineered red-shifted very-fast-Chrimson (vf-Chrimson-ES/TS) which has similar fast kinetics as fast as Chronos-ES/TS, evoked fast responses until 500 Hz stimulation rate from the mouse AN. Moreover, we further characterized light intensity encoding of vf-Chrimson-ES/TS in comparison to the slower variant fast-Chrimson (f-Chrimson). Third, we studied the long-term availability and biosafety profile of f-Chrimson, a prominent candidate for use with the optical CI, showing expression in SGNs up to two years following early postnatal AAV-based delivery to the inner ear.There was also a tendency of SGN loss due to combinatorial effect of aging and f-Chrimson expression. Expression spread to the non-injection ear and parts of the brain. The spread was restricted to the vicinity of injection and was not detected in the distal organs such as kidney and spleen. All in all, these three projects that I was involved in at different extents pave the way to future medical optogenetic cochlear implants.

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

Cited by 5 publications

References 79 publications

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

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

A dual-channel optogenetic stimulator selectively modulates distinct defensive behaviors

Optogenetic Manipulation of the Auditory System

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