Therapeutic AAV Gene Transfer to the Nervous System: A Clinical Reality

Neuron, Journal Year: 2019, Volume and Issue: 101(5), P. 839 - 862

Published: March 1, 2019

Language: Английский

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Towards translational optogenetics

Nature Biomedical Engineering, Journal Year: 2022, Volume and Issue: 7(4), P. 349 - 369

Published: Jan. 13, 2022

Language: Английский

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Cochlear Implant Research and Development in the Twenty-first Century: A Critical Update

Journal of the Association for Research in Otolaryngology, Journal Year: 2021, Volume and Issue: 22(5), P. 481 - 508

Published: Aug. 25, 2021

Abstract Cochlear implants (CIs) are the world’s most successful sensory prosthesis and have been subject of intense research development in recent decades. We critically review progress CI research, its success improving patient outcomes, from turn century to present day. The focuses on processing, stimulation, audiological methods that used try improve speech perception by human listeners, fundamental new insights response auditory system electrical stimulation. introduction directional microphones noise reduction pre-processing algorithms has produced robust sometimes substantial improvements. Novel speech-processing algorithms, use current-focusing methods, individualised (patient-by-patient) deactivation subsets electrodes more modest argue incremental advances will continue be made, collectively these may substantially but size each individual advance require greater attention experimental design power. also briefly discuss potential limitations promising technologies currently being developed animal models, suggest strategies for researchers maximise CIs hearing a wide range listening situations.

Language: Английский

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Towards the optical cochlear implant: optogenetic approaches for hearing restoration

EMBO Molecular Medicine, Journal Year: 2020, Volume and Issue: 12(4)

Published: March 30, 2020

Cochlear implants (CIs) are considered the most successful neuroprosthesis as they enable speech comprehension in majority of half a million CI users suffering from sensorineural hearing loss. By electrically stimulating auditory nerve, CIs constitute an interface re-connecting brain and scene, providing patient with information regarding latter. However, since electric current is hard to focus conductive environments such cochlea, precision electrical sound encoding-and thus quality artificial hearing-is limited. Recently, optogenetic stimulation cochlea has been suggested alternative approach for restoration. optogenetics promises increased spectral selectivity encoding, hence improved hearing, light can conveniently be confined space activate nerve within smaller tonotopic ranges. In this review, we discuss latest experimental technological developments cochlear outline remaining challenges on way clinical translation.

Language: Английский

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Near physiological spectral selectivity of cochlear optogenetics

Nature Communications, Journal Year: 2019, Volume and Issue: 10(1)

Published: April 29, 2019

Abstract Cochlear implants (CIs) electrically stimulate spiral ganglion neurons (SGNs) and partially restore hearing to half a million CI users. However, wide current spread from intracochlear electrodes limits spatial selectivity (i.e. spectral resolution) of electrical CIs. Optogenetic stimulation might become an alternative, since light can be confined in space, promising artificial sound encoding with increased selectivity. Here we compare optogenetic, electric, acoustic by multi-channel recordings the inferior colliculus (IC) gerbils. When projecting onto tonotopically distinct SGNs, observe corresponding ordered IC activity. An activity-based comparison reveals that optogenetic is indistinguishable for modest intensities. Moreover, outperforms bipolar electric at medium high intensities monopolar all In conclusion, demonstrate better over SGN stimulation, suggesting potential improved restoration optical

Language: Английский

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

Science Translational Medicine, Journal Year: 2020, Volume and Issue: 12(553)

Published: July 22, 2020

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

Language: Английский

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The multi-stage plasticity in the aggression circuit underlying the winner effect

Cell, Journal Year: 2024, Volume and Issue: 187(24), P. 6785 - 6803.e18

Published: Oct. 14, 2024

Language: Английский

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New molecular therapies for the treatment of hearing loss

Pharmacology & Therapeutics, Journal Year: 2019, Volume and Issue: 200, P. 190 - 209

Published: May 8, 2019

Language: Английский

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Primate optogenetics: Progress and prognosis

Proceedings of the National Academy of Sciences, Journal Year: 2019, Volume and Issue: 116(52), P. 26195 - 26203

Published: Dec. 23, 2019

Monkeys are a premier model organism for neuroscience research. Activity in the central nervous systems of monkeys can be recorded and manipulated while they perform complex perceptual, motor, or cognitive tasks. Conventional techniques manipulating neural activity too coarse to address many outstanding questions primate neuroscience, but optogenetics holds promise overcome this hurdle. In article, we review progress that has been made over past 5 years. We emphasize use gene regulatory sequences viral vectors target specific neuronal types, present data on engineered parvalbumin-expressing neurons. conclude with discussion utility treating sensorimotor hearing loss Parkinson's disease, areas translational which provide unique leverage basic science medicine.

Language: Английский

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Efficient viral transduction in mouse inner ear hair cells with utricle injection and AAV9-PHP.B

Hearing Research, Journal Year: 2020, Volume and Issue: 394, P. 107882 - 107882

Published: Jan. 13, 2020

Viral delivery of exogenous coding sequences into the inner ear has potential for therapeutic benefit patients suffering genetic or acquired hearing loss. To devise improved strategies viral delivery, we investigated two injection techniques, round window membrane a novel utricle method, their ability to safely and efficiently transduce sensory hair cells neurons mouse ear. In addition, evaluated three synthetic AAV vectors (Anc80L65, AAV9-PHP.B, AAV2.7m8) encoding enhanced green fluorescent protein (eGFP) promoters (Cmv, Synapsin, Gfap) drive expression in desired cell types. We found method with AAV9-PHP.B Cmv promoter was most efficient combination driving robust eGFP both outer cells. levels rose over 3–5 days post-injection, dose 1.5 × 109 gc yielded half maximal that transduced even when delivered as late postnatal day 16. Sensory transduction auditory thresholds were unaltered injected mice relative uninjected wild-type controls. Vestibular end organs also without affecting balance behavior. The Synapsin Gfap drove strong supporting cells, respectively. conclude vector are well-suited gene constructs ears models vestibular dysfunction.

Language: Английский

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