نبذة مختصرة : This is the final version. Available on open access from Wiley via the DOI in this record ; Data availability: Data have not been deposited in an external public repository but can be shared on reasonable request to the corresponding author. ; 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. ; Human Frontier Science Program ; Medical Research Council (MRC) ; Polish National Agency for Academic Exchange ; National Centre for the Replacement Refinement & Reduction of Animals in Research ; Fight for Sight ; Biotechnology and Biological Sciences Research Council (BBSRC)
Processing Request
No Comments.