A photoswitchable GPCR-based opsin for presynaptic inhibition

Copits, Bryan A; Gowrishankar, Raaj; O’Neill, Patrick R; Li, Jun-Nan; Girven, Kasey S; Yoo, Judy J; Meshik, Xenia; Parker, Kyle E; Spangler, Skylar M; Elerding, Abigail J; Brown, Bobbie J; Shirley, Sofia E; Ma, Kelly K L; Vasquez, Alexis M; Stander, M Christine; Kalyanaraman, Vani; Vogt, Sherri K; Samineni, Vijay K; Patriarchi, Tommaso; Tian, Lin

doi:10.1016/j.neuron.2021.04.026

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Copits, B. A., Gowrishankar, R., O’Neill, P. R., Li, J.-N., Girven, K. S., Yoo, J. J., Meshik, X., Parker, K. E., Spangler, S. M., Elerding, A. J., Brown, B. J., Shirley, S. E., Ma, K. K. L., Vasquez, A. M., Stander, M. C., Kalyanaraman, V., Vogt, S. K., Samineni, V. K., Patriarchi, T., … Bruchas, M. R. (2021). A photoswitchable GPCR-based opsin for presynaptic inhibition. Neuron, 109(11), 1791-1809.e11. https://doi.org/10.1016/j.neuron.2021.04.026

Abstract

Optical manipulations of genetically defined cell types have generated significant insights into the dynamics of neural circuits. While optogenetic activation has been relatively straightforward, rapid and reversible synaptic inhibition has proven more elusive. Here, we leveraged the natural ability of inhibitory presynaptic GPCRs to suppress synaptic transmission and characterize parapinopsin (PPO) as a GPCR-based opsin for terminal inhibition. PPO is a photoswitchable opsin that couples to Gi/o signaling cascades and is rapidly acti