Optogenetically modified human embryonic stem cell-derived otic neurons establish functional synaptic connection with cochlear nuclei DOI Creative Commons
Yanni Chen,

Wenbo Mu,

Yongkang Wu

et al.

Journal of Tissue Engineering, Journal Year: 2024, Volume and Issue: 15

Published: Jan. 1, 2024

Spiral ganglia neurons (SGNs) impairment can cause deafness. One important therapeutic approach involves utilizing stem cells to restore impaired auditory circuitry. Nevertheless, the inadequate implementation of research methodologies poses a challenge in accurately assessing functionality derived within circuit. Here, we describe novel method for converting human embryonic (hESCs) into otic (ONs) and assess their functional connectivity using an optogenetic with or organotypic slice rat cochlear nucleus (CN) coculture. Embryonic cell-derived (eONs) exhibited SGN marker expression generated synaptic connection when cocultured (CNNs). Synapsin 1 VGLUT are found brain slices, where eONs projected processes during coculture CN slices. Action potential spikes I Na+ /I K+ CNNs increased tandem light stimulations eONs. These findings provide further evidence that may be candidate source treat SGN-deafness.

Language: Английский

Toward Optogenetic Hearing Restoration DOI
Antoine Huet, Thomas Mager, Christian Goßler

et al.

Annual Review of Neuroscience, Journal Year: 2024, Volume and Issue: 47(1), P. 103 - 121

Published: April 10, 2024

The cochlear implant (CI) is considered the most successful neuroprosthesis as it enables speech comprehension in majority of million otherwise deaf patients. In hearing by electrical stimulation auditory nerve, broad spread current from each electrode acts a bottleneck that limits transfer sound frequency information. Hence, there remains major unmet medical need for improving quality with CIs. Recently, optogenetic cochlea has been suggested an alternative approach restoration. Cochlear optogenetics promises to more information, hence hearing, light can conveniently be confined space activate nerve within smaller tonotopic ranges. this review, we discuss latest experimental and technological developments restoration outline remaining challenges en route clinical translation.

Language: Английский

Citations

7
Intracellular microbial rhodopsin-based optogenetics to control metabolism and cell signaling DOI Creative Commons
Anastasiia D. Vlasova, Siarhei Bukhalovich, Diana F. Bagaeva

et al.

Chemical Society Reviews, Journal Year: 2024, Volume and Issue: 53(7), P. 3327 - 3349

Published: Jan. 1, 2024

Organelle optogenetics is an approach to control cell physiology by targeted expression of microbial rhodopsins in membranes subcellular organelles.

Language: Английский

Citations

5
Genetically‐targeted control of the spinal cord and peripheral nervous system DOI Creative Commons
Anakaren Romero-Lozano,

Victoria Koptelova,

Zoya Ahmad

et al.

Journal of intelligent medicine., Journal Year: 2025, Volume and Issue: unknown

Published: April 22, 2025

Abstract Genetically‐targeted neuromodulation, such as opto‐ or chemogenetics, is important for cell‐type specific neuromodulation different applications. Modulating peripheral nerves a daunting task due to the wide variety of constraints in periphery, size, location, and relative distance other nerves. This has resulted many researchers developing innovative solutions modulate nerves, including types light‐emitting devices optogenetics, ligands designer drugs (DREADDs) use nanotechnology. Although spinal cord part central nervous system, it often site stimulation modulating function periphery anatomy same obstacles modulation review summarizes current efforts genetically‐targeted grouped by applications, going through major areas which advancements have been made. We focus on vivo research rodents but also briefly discuss work nonhuman primates (NHPs). Some clinical translation, long‐term adeno‐associated virus (AAV) safety, are discussed some noninvasive, nonspecific technologies mentioned.

Language: Английский

Citations

0
Efficient and sustained optogenetic control of nervous and cardiac systems DOI Open Access
Alexey Alekseev, Victoria Hunniford,

Maria Zerche

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Nov. 18, 2023

Abstract Optogenetic control of cells is a key life sciences method and promises novel therapies. Here we report on ChReef, an improved variant the channelrhodopsin ChRmine. ChReef offers minimal photocurrent desensitization, unitary conductance 80 fS closing kinetics 30 ms, which together enable reliable optogenetic at low light levels (nano-Joule) with good temporal fidelity allows sustained stimulation. We demonstrate efficient red-light pacing depolarization block ChReef-expressing cardiomyocyte clusters. Towards clinical application used AAV-based gene transfer to express in retinal ganglion where it restores visual function blind mice sources as weak iPad screen. Toward hearing restoration, enables stimulation auditory pathway rodents non-human primates nano-Joule threshold enabling frequency-specific by LED-based optical cochlear implants. Thus, bears great potential for application.

Language: Английский

Citations

3
Devising a framework of optogenetic coding in the auditory pathway: Insights from auditory midbrain recordings DOI Creative Commons
M Halassa Michael, Bettina Wolf,

Astrid Klinge‐Strahl

et al.

Brain stimulation, Journal Year: 2023, Volume and Issue: 16(5), P. 1486 - 1500

Published: Sept. 1, 2023

Cochlear implants (CIs) restore activity in the deafened auditory system via electrical stimulation of nerve. As spread electric current biological tissues is rather broad, spectral information provided by CIs limited. Optogenetic nerve has been suggested for artificial sound coding with improved selectivity, as light can be conveniently confined space. Yet, foundations optogenetic strategies remain to established. Here, we parametrized stimulus-response-relationships pathway gerbils stimulation. Upon activation waveguide-based spiral ganglion, recorded neuronal midbrain, which neural representations spectral, temporal, and intensity found. Screening a wide range optical stimuli taking properties CI emitters into account, aimed optimize stimulus paradigms potent energy-efficient pathway. We report that efficient builds on integration millisecond built from microsecond pulses, optimally accommodate power-efficient laser diode operation. Moreover, performed an activity-level-dependent comparison acoustic order estimate dynamic maximal amenable single channel encoding, indicate it complies well speech comprehension typical conversation (65 dB). Our results provide first framework development future hearing restoration.

Language: Английский

Citations

2
Improved optogenetic modification of the spiral ganglion neurons for future optical cochlear implants DOI Creative Commons
Anupriya Thirumalai, Jörg Henseler,

Marzieh Enayati

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 12, 2024

Abstract Optogenetic stimulation has become a promising approach for restoring lost body function. For example, partial restoration of vision been achieved in blind patient and proof-of-concept demonstrated optogenetic hearing rodents. In order to prepare clinical translation restoration, efficient safe modification spiral ganglion neurons (SGNs) the mature cochlea remains be developed. Here, we established microcatheter-based administration adeno-associated virus (AAV) scala tympani Mongolian gerbils compared it previously developed AAV-injection into ganglion. We probed potential AAV-PHP.S capsid express channelrhodopsins (ChRs) under control human synapsin promotor SGNs deafened gerbils. Using microcatheter approach, but not with AAV-modiolus injection, reliable ChR expression SGN enabling auditory pathway 80% treated animals. Yet, efficiency transduction was modest only ∼30% ChR-expressing SGNs. Moreover, encountered off-target hair cells both approaches, central nervous system using administration. Comparing brainstem responses without cell confirmed that were primary site pathway.

Language: Английский

Citations

0
En route to sound coding strategies for optical cochlear implants DOI Creative Commons
Lakshay Khurana, Tamás Harczos, Tobias Moser

et al.

iScience, Journal Year: 2023, Volume and Issue: 26(10), P. 107725 - 107725

Published: Aug. 26, 2023

Hearing loss is the most common human sensory deficit. Severe-to-complete sensorineural hearing often treated by electrical cochlear implants (eCIs) bypassing dysfunctional or lost hair cells direct stimulation of auditory nerve. The wide current spread from each intracochlear electrode array contact activates large sets tonotopically organized neurons limiting spectral selectivity sound coding. Despite many efforts, an increase in number independent eCI channels seems impossible to achieve. Light, which can be better confined space than electric may help optical (oCIs) overcome shortcomings. In this review, we present state optogenetic encoding. We highlight coding strategy development capitalizing on that requires fine-grained, fast, and power-efficient real-time processing controlling dozens microscale emitters as emerging research area.

Language: Английский

Citations

1
Decreasing the physical gap in the neural-electrode interface and related concepts to improve cochlear implant performance DOI Creative Commons
Joseph T. Vecchi, Alexander D. Claussen, Marlan R. Hansen

et al.

Frontiers in Neuroscience, Journal Year: 2024, Volume and Issue: 18

Published: July 24, 2024

Cochlear implants (CI) represent incredible devices that restore hearing perception for those with moderate to profound sensorineural loss. However, the ability of a CI complex auditory function is limited by number perceptually independent spectral channels provided. A major contributor this limitation physical gap between electrodes and target spiral ganglion neurons (SGNs). In order stimulate SGNs more precisely, thus better approximate natural hearing, new methodologies need be developed decrease gap, (i.e., transitioning CIs from far-field near-field device). review, strategies aimed at improving neural-electrode interface are discussed in terms magnitude impact they could have work needed implement them. Ongoing research suggests current clinical efforts limit CI-related immune response holds great potential device performance. This eradicate dense, fibrous capsule surrounding electrode enhance preservation cochlear architecture, including SGNs. long term, however, optimized future will likely induce guide outgrowth peripheral process closer proximity hearing. its infancy; it remains seen which (surface patterning, small molecule release, hydrogel coating, etc.) enable approach. Additionally, these optimizing translate other neural prostheses, face similar issues.

Language: Английский

Citations

0
Optogenetically modified human embryonic stem cell-derived otic neurons establish functional synaptic connection with cochlear nuclei DOI Creative Commons
Yanni Chen,

Wenbo Mu,

Yongkang Wu

et al.

Journal of Tissue Engineering, Journal Year: 2024, Volume and Issue: 15

Published: Jan. 1, 2024

Spiral ganglia neurons (SGNs) impairment can cause deafness. One important therapeutic approach involves utilizing stem cells to restore impaired auditory circuitry. Nevertheless, the inadequate implementation of research methodologies poses a challenge in accurately assessing functionality derived within circuit. Here, we describe novel method for converting human embryonic (hESCs) into otic (ONs) and assess their functional connectivity using an optogenetic with or organotypic slice rat cochlear nucleus (CN) coculture. Embryonic cell-derived (eONs) exhibited SGN marker expression generated synaptic connection when cocultured (CNNs). Synapsin 1 VGLUT are found brain slices, where eONs projected processes during coculture CN slices. Action potential spikes I Na+ /I K+ CNNs increased tandem light stimulations eONs. These findings provide further evidence that may be candidate source treat SGN-deafness.

Language: Английский

Citations

0