Viral-mediated transduction of auditory neurons with opsins for optical and hybrid activation

Abstract Optical stimulation is a paradigm-shifting approach to modulating neural activity that has the potential to overcome the issue of current spread that occurs with electrical stimulation by providing focused stimuli. But optical stimulation either requires high power infrared light or genetic...

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Autores principales:	Rachael T. Richardson, Alex C. Thompson, Andrew K. Wise, Elise A. Ajay, Niliksha Gunewardene, Stephen J. O’Leary, Paul R. Stoddart, James B. Fallon
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/07f2283027834332ac810d3131bfc53f
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spelling	oai:doaj.org-article:07f2283027834332ac810d3131bfc53f2021-12-02T15:00:55ZViral-mediated transduction of auditory neurons with opsins for optical and hybrid activation10.1038/s41598-021-90764-92045-2322https://doaj.org/article/07f2283027834332ac810d3131bfc53f2021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-90764-9https://doaj.org/toc/2045-2322Abstract Optical stimulation is a paradigm-shifting approach to modulating neural activity that has the potential to overcome the issue of current spread that occurs with electrical stimulation by providing focused stimuli. But optical stimulation either requires high power infrared light or genetic modification of neurons to make them responsive to lower power visible light. This work examines optical activation of auditory neurons following optogenetic modification via AAV injection in two species (mouse and guinea pig). An Anc80 viral vector was used to express the channelrhodopsin variant ChR2-H134R fused to a fluorescent reporter gene under the control of the human synapsin-1 promoter. The AAV was administered directly to the cochlea (n = 33) or posterior semi-circular canal of C57BL/6 mice (n = 4) or to guinea pig cochleae (n = 6). Light (488 nm), electrical stimuli or the combination of these (hybrid stimulation) was delivered to the cochlea via a laser-coupled optical fibre and co-located platinum wire. Activation thresholds, spread of activation and stimulus interactions were obtained from multi-unit recordings from the central nucleus of the inferior colliculus of injected mice, as well as ChR2-H134R transgenic mice (n = 4). Expression of ChR2-H134R was examined by histology. In the mouse, transduction of auditory neurons by the Anc80 viral vector was most successful when injected at a neonatal age with up to 89% of neurons transduced. Auditory neuron transductions were not successful in guinea pigs. Inferior colliculus responses to optical stimuli were detected in a cochleotopic manner in all mice with ChR2-H134R expression. There was a significant correlation between lower activation thresholds in mice and higher proportions of transduced neurons. There was no difference in spread of activation between optical stimulation and electrical stimulation provided by the light/electrical delivery system used here (optical fibre with bonded 25 µm platinum/iridium wire). Hybrid stimulation, comprised of sub-threshold optical stimulation to ‘prime’ or raise the excitability of the neurons, lowered the threshold for electrical activation in most cases, but the impact on excitation width was more variable compared to transgenic mice. This study demonstrates the impact of opsin expression levels and expression pattern on optical and hybrid stimulation when considering optical or hybrid stimulation techniques for neuromodulation.Rachael T. RichardsonAlex C. ThompsonAndrew K. WiseElise A. AjayNiliksha GunewardeneStephen J. O’LearyPaul R. StoddartJames B. FallonNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-17 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Rachael T. Richardson Alex C. Thompson Andrew K. Wise Elise A. Ajay Niliksha Gunewardene Stephen J. O’Leary Paul R. Stoddart James B. Fallon Viral-mediated transduction of auditory neurons with opsins for optical and hybrid activation
description	Abstract Optical stimulation is a paradigm-shifting approach to modulating neural activity that has the potential to overcome the issue of current spread that occurs with electrical stimulation by providing focused stimuli. But optical stimulation either requires high power infrared light or genetic modification of neurons to make them responsive to lower power visible light. This work examines optical activation of auditory neurons following optogenetic modification via AAV injection in two species (mouse and guinea pig). An Anc80 viral vector was used to express the channelrhodopsin variant ChR2-H134R fused to a fluorescent reporter gene under the control of the human synapsin-1 promoter. The AAV was administered directly to the cochlea (n = 33) or posterior semi-circular canal of C57BL/6 mice (n = 4) or to guinea pig cochleae (n = 6). Light (488 nm), electrical stimuli or the combination of these (hybrid stimulation) was delivered to the cochlea via a laser-coupled optical fibre and co-located platinum wire. Activation thresholds, spread of activation and stimulus interactions were obtained from multi-unit recordings from the central nucleus of the inferior colliculus of injected mice, as well as ChR2-H134R transgenic mice (n = 4). Expression of ChR2-H134R was examined by histology. In the mouse, transduction of auditory neurons by the Anc80 viral vector was most successful when injected at a neonatal age with up to 89% of neurons transduced. Auditory neuron transductions were not successful in guinea pigs. Inferior colliculus responses to optical stimuli were detected in a cochleotopic manner in all mice with ChR2-H134R expression. There was a significant correlation between lower activation thresholds in mice and higher proportions of transduced neurons. There was no difference in spread of activation between optical stimulation and electrical stimulation provided by the light/electrical delivery system used here (optical fibre with bonded 25 µm platinum/iridium wire). Hybrid stimulation, comprised of sub-threshold optical stimulation to ‘prime’ or raise the excitability of the neurons, lowered the threshold for electrical activation in most cases, but the impact on excitation width was more variable compared to transgenic mice. This study demonstrates the impact of opsin expression levels and expression pattern on optical and hybrid stimulation when considering optical or hybrid stimulation techniques for neuromodulation.
format	article
author	Rachael T. Richardson Alex C. Thompson Andrew K. Wise Elise A. Ajay Niliksha Gunewardene Stephen J. O’Leary Paul R. Stoddart James B. Fallon
author_facet	Rachael T. Richardson Alex C. Thompson Andrew K. Wise Elise A. Ajay Niliksha Gunewardene Stephen J. O’Leary Paul R. Stoddart James B. Fallon
author_sort	Rachael T. Richardson
title	Viral-mediated transduction of auditory neurons with opsins for optical and hybrid activation
title_short	Viral-mediated transduction of auditory neurons with opsins for optical and hybrid activation
title_full	Viral-mediated transduction of auditory neurons with opsins for optical and hybrid activation
title_fullStr	Viral-mediated transduction of auditory neurons with opsins for optical and hybrid activation
title_full_unstemmed	Viral-mediated transduction of auditory neurons with opsins for optical and hybrid activation
title_sort	viral-mediated transduction of auditory neurons with opsins for optical and hybrid activation
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/07f2283027834332ac810d3131bfc53f
work_keys_str_mv	AT rachaeltrichardson viralmediatedtransductionofauditoryneuronswithopsinsforopticalandhybridactivation AT alexcthompson viralmediatedtransductionofauditoryneuronswithopsinsforopticalandhybridactivation AT andrewkwise viralmediatedtransductionofauditoryneuronswithopsinsforopticalandhybridactivation AT eliseaajay viralmediatedtransductionofauditoryneuronswithopsinsforopticalandhybridactivation AT nilikshagunewardene viralmediatedtransductionofauditoryneuronswithopsinsforopticalandhybridactivation AT stephenjoleary viralmediatedtransductionofauditoryneuronswithopsinsforopticalandhybridactivation AT paulrstoddart viralmediatedtransductionofauditoryneuronswithopsinsforopticalandhybridactivation AT jamesbfallon viralmediatedtransductionofauditoryneuronswithopsinsforopticalandhybridactivation
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Viral-mediated transduction of auditory neurons with opsins for optical and hybrid activation

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