Using a bistable animal opsin for switchable and scalable optogenetic inhibition of neurons.

Autor: Rodgers J; Faculty of Biology Medicine and Health, University of Manchester, Manchester, UK., Bano-Otalora B; Faculty of Biology Medicine and Health, University of Manchester, Manchester, UK., Belle MDC; Institute of Biomedical and Clinical Sciences, University of Exeter Medical School, University of Exeter, Exeter, UK., Paul S; Faculty of Biology Medicine and Health, University of Manchester, Manchester, UK., Hughes R; Faculty of Biology Medicine and Health, University of Manchester, Manchester, UK., Wright P; Faculty of Biology Medicine and Health, University of Manchester, Manchester, UK., McDowell R; Faculty of Biology Medicine and Health, University of Manchester, Manchester, UK., Milosavljevic N; Faculty of Biology Medicine and Health, University of Manchester, Manchester, UK., Orlowska-Feuer P; Faculty of Biology Medicine and Health, University of Manchester, Manchester, UK.; Department of Neurophysiology and Chronobiology, Institute of Zoology and Biomedical Research, Jagiellonian University in Krakow, Krakow, Poland., Martial FP; Faculty of Biology Medicine and Health, University of Manchester, Manchester, UK., Wynne J; Faculty of Biology Medicine and Health, University of Manchester, Manchester, UK., Ballister ER; Faculty of Biology Medicine and Health, University of Manchester, Manchester, UK.; Department of Biomedical Engineering, Columbia University, New York, NY, USA., Storchi R; Faculty of Biology Medicine and Health, University of Manchester, Manchester, UK., Allen AE; Faculty of Biology Medicine and Health, University of Manchester, Manchester, UK., Brown T; Faculty of Biology Medicine and Health, University of Manchester, Manchester, UK., Lucas RJ; Faculty of Biology Medicine and Health, University of Manchester, Manchester, UK.
Jazyk: angličtina
Zdroj: EMBO reports [EMBO Rep] 2021 May 05; Vol. 22 (5), pp. e51866. Date of Electronic Publication: 2021 Mar 02.
DOI: 10.15252/embr.202051866
Abstrakt: There is no consensus on the best inhibitory optogenetic tool. Since Gi/o signalling is a native mechanism of neuronal inhibition, we asked whether Lamprey Parapinopsin ("Lamplight"), a Gi/o-coupled bistable animal opsin, could be used for optogenetic silencing. We show that short (405 nm) and long (525 nm) wavelength pulses repeatedly switch Lamplight between stable signalling active and inactive states, respectively, and that combining these wavelengths can be used to achieve intermediate levels of activity. These properties can be applied to produce switchable neuronal hyperpolarisation and suppression of spontaneous spike firing in the mouse hypothalamic suprachiasmatic nucleus. Expressing Lamplight in (predominantly) ON bipolar cells can photosensitise retinas following advanced photoreceptor degeneration, with 405 and 525 nm stimuli producing responses of opposite sign in the output neurons of the retina. We conclude that bistable animal opsins can co-opt endogenous signalling mechanisms to allow optogenetic inhibition that is scalable, sustained and reversible.
(© 2021 The Authors. Published under the terms of the CC BY 4.0 license.)
Databáze: MEDLINE
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