A bistable inhibitory OptoGPCR for multiplexed optogenetic control of neural circuits
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A bistable inhibitory OptoGPCR for multiplexed optogenetic control of neural circuits. / Wietek, Jonas; Nozownik, Adrianna; Pulin, Mauro; Saraf-Sinik, Inbar; Matosevich, Noa; Malan, Daniela; Brown, Bobbie J; Dine, Julien; Levy, Rivka; Litvin, Anna; Regev, Noa; Subramaniam, Suraj; Bitton, Eyal; Benjamin, Asaf; Copits, Bryan A; Sasse, Philipp; Rost, Benjamin R; Schmitz, Dietmar; Soba, Peter; Nir, Yuval; Wiegert, J Simon; Yizhar, Ofer.
In: bioRxiv, 02.07.2023.Research output: SCORING: Contribution to journal › Preprint › Research
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TY - JOUR
T1 - A bistable inhibitory OptoGPCR for multiplexed optogenetic control of neural circuits
AU - Wietek, Jonas
AU - Nozownik, Adrianna
AU - Pulin, Mauro
AU - Saraf-Sinik, Inbar
AU - Matosevich, Noa
AU - Malan, Daniela
AU - Brown, Bobbie J
AU - Dine, Julien
AU - Levy, Rivka
AU - Litvin, Anna
AU - Regev, Noa
AU - Subramaniam, Suraj
AU - Bitton, Eyal
AU - Benjamin, Asaf
AU - Copits, Bryan A
AU - Sasse, Philipp
AU - Rost, Benjamin R
AU - Schmitz, Dietmar
AU - Soba, Peter
AU - Nir, Yuval
AU - Wiegert, J Simon
AU - Yizhar, Ofer
PY - 2023/7/2
Y1 - 2023/7/2
N2 - 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 (GPCRs) 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 GPCR that can suppress synaptic transmission in mammalian neurons with high temporal precision in-vivo. PdCO has superior 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.
AB - 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 (GPCRs) 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 GPCR that can suppress synaptic transmission in mammalian neurons with high temporal precision in-vivo. PdCO has superior 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.
U2 - 10.1101/2023.07.01.547328
DO - 10.1101/2023.07.01.547328
M3 - Preprint
C2 - 37425961
JO - bioRxiv
JF - bioRxiv
SN - 2692-8205
ER -