Using a bistable animal opsin for switchable and scalable optogenetic inhibition of neurons.
GPCR
bistable
neuronal inhibition
opsins
optogenetics
Journal
EMBO reports
ISSN: 1469-3178
Titre abrégé: EMBO Rep
Pays: England
ID NLM: 100963049
Informations de publication
Date de publication:
05 05 2021
05 05 2021
Historique:
revised:
29
01
2021
received:
09
10
2020
accepted:
02
02
2021
pubmed:
4
3
2021
medline:
1
6
2021
entrez:
3
3
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 33655694
doi: 10.15252/embr.202051866
pmc: PMC8097317
doi:
Substances chimiques
Opsins
0
Rod Opsins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e51866Subventions
Organisme : Medical Research Council
ID : MR/N012992/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/S026266/1
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/S01764X/1
Pays : United Kingdom
Informations de copyright
© 2021 The Authors. Published under the terms of the CC BY 4.0 license.
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