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Abstract
Optogenetic manipulation of neuronal activity through excitatory and inhibitory opsins has become an indispensable experimental strategy in neuroscience research. For many applications bidirectional control of neuronal activity allowing both excitation and inhibition of the same neurons in a single experiment is desired. This requires low spectral overlap between the excitatory and inhibitory opsin, matched photocurrent amplitudes and a fixed expression ratio. Moreover, independent activation of two distinct neuronal populations with different optogenetic actuators is still challenging due to blue-light sensitivity of all opsins. Here we report BiPOLES, an optogenetic tool for potent neuronal excitation and inhibition with light of two different wavelengths. BiPOLES enables sensitive, reliable dual-color neuronal spiking and silencing with single- or two-photon excitation, optical tuning of the membrane voltage, and independent optogenetic control of two neuronal populations using a second, blue-light sensitive opsin. The utility of BiPOLES is demonstrated in worms, flies, mice and ferrets.
Currently, bidirectional control of activity in the same neurons in the same experiment is difficult. Here the authors report a Bidirectional Pair of Opsins for Light-induced Excitation and Silencing, BiPOLES, which they use in a range of organisms including worms, fruit flies, mice and ferrets.
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1 Humboldt University Berlin, Institute for Biology, Experimental Biophysics, Berlin, Germany (GRID:grid.7468.d) (ISNI:0000 0001 2248 7639)
2 University Medical Center Hamburg-Eppendorf, Research Group Synaptic Wiring and Information Processing, Center for Molecular Neurobiology Hamburg, Hamburg, Germany (GRID:grid.13648.38) (ISNI:0000 0001 2180 3484)
3 University Medical Center Hamburg-Eppendorf, Department of Neurophysiology and Pathophysiology, Hamburg, Germany (GRID:grid.13648.38) (ISNI:0000 0001 2180 3484)
4 Sorbonne Université, INSERM, CNRS, Institut de la Vision, Wavefront-Engineering Microscopy Group, Photonics Department, Institut de la Vision, Paris, France (GRID:grid.418241.a) (ISNI:0000 0000 9373 1902)
5 University Medical Center Hamburg-Eppendorf, Research Group Neuronal Patterning and Connectivity, Center for Molecular Neurobiology Hamburg, Hamburg, Germany (GRID:grid.13648.38) (ISNI:0000 0001 2180 3484)
6 Goethe University, Buchmann Institute for Molecular Life Sciences and Institute of Biophysical Chemistry, Frankfurt, Germany (GRID:grid.7839.5) (ISNI:0000 0004 1936 9721)
7 University Medical Center Hamburg-Eppendorf, Research Group Synaptic Wiring and Information Processing, Center for Molecular Neurobiology Hamburg, Hamburg, Germany (GRID:grid.13648.38) (ISNI:0000 0001 2180 3484); University Medical Center Hamburg-Eppendorf, Research Group Neuronal Patterning and Connectivity, Center for Molecular Neurobiology Hamburg, Hamburg, Germany (GRID:grid.13648.38) (ISNI:0000 0001 2180 3484)
8 University Medical Center Hamburg-Eppendorf, Research Group Neuronal Patterning and Connectivity, Center for Molecular Neurobiology Hamburg, Hamburg, Germany (GRID:grid.13648.38) (ISNI:0000 0001 2180 3484); University of Bonn, LIMES Institute, Bonn, Germany (GRID:grid.10388.32) (ISNI:0000 0001 2240 3300)