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| Item Type: | Article |
|---|---|
| Title: | A bistable inhibitory optoGPCR for multiplexed optogenetic control of neural circuits |
| Creators Name: | Wietek, J. and Nozownik, A. and Pulin, M. and Saraf-Sinik, I. and Matosevich, N. and Gowrishankar, R. and Gat, A. and Malan, D. and Brown, B.J. and Dine, J. and Imambocus, B.N. and Levy, R. and Sauter, K. and Litvin, A. and Regev, N. and Subramaniam, S. and Abrera, K. and Summarli, D. and Goren, E.M. and Mizrachi, G. and Bitton, E. and Benjamin, A. and Copits, B.A. and Sasse, P. and Rost, B.R. and Schmitz, D. and Bruchas, M.R. and Soba, P. and Oren-Suissa, M. and Nir, Y. and Wiegert, J.S. and Yizhar, O. |
| Abstract: | Information is transmitted between brain regions through the release of neurotransmitters from long-range projecting axons. Understanding how the activity of such long-range connections contributes to behavior requires efficient methods for reversibly manipulating their function. Chemogenetic and optogenetic tools, acting through endogenous G-protein-coupled receptor pathways, can be used to modulate synaptic transmission, but existing tools are limited in sensitivity, spatiotemporal precision or spectral multiplexing capabilities. Here we systematically evaluated multiple bistable opsins for optogenetic applications and found that the Platynereis dumerilii ciliary opsin (PdCO) is an efficient, versatile, light-activated bistable G-protein-coupled receptor that can suppress synaptic transmission in mammalian neurons with high temporal precision in vivo. PdCO has useful biophysical properties that enable spectral multiplexing with other optogenetic actuators and reporters. We demonstrate that PdCO can be used to conduct reversible loss-of-function experiments in long-range projections of behaving animals, thereby enabling detailed synapse-specific functional circuit mapping. |
| Keywords: | Molecular Neuroscience, Neurophysiology, Synaptic Transmission, Animals, Mice |
| Source: | Nature Methods |
| ISSN: | 1548-7091 |
| Publisher: | Nature Publishing Group |
| Date: | 29 May 2024 |
| Official Publication: | https://doi.org/10.1038/s41592-024-02285-8 |
| PubMed: | View item in PubMed |
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