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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2021-05-27

AUTHORS

Rachael T. Richardson, Alex C. Thompson, Andrew K. Wise, Elise A. Ajay, Niliksha Gunewardene, Stephen J. O’Leary, Paul R. Stoddart, James B. Fallon

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. More... »

PAGES

11229

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41598-021-90764-9

DOI

http://dx.doi.org/10.1038/s41598-021-90764-9

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1138393938

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/34045604


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104 power
105 primes
106 promoter
107 proportion
108 recordings
109 reporter gene
110 response
111 semi-circular canals
112 significant correlation
113 species
114 spread
115 spread of activation
116 stimulation
117 stimulation techniques
118 stimuli
119 stimulus interaction
120 study
121 synapsin-1 promoter
122 system
123 technique
124 threshold
125 transduction
126 transgenic mice
127 vector
128 viral
129 viral vectors
130 visible light
131 width
132 wire
133 work
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