24997763

PMC4184214

1DP2NS082126/DP/NCCDPHP CDC HHS/United States
1DP2OD002002/OD/NIH HHS/United States
1R01DA029639/DA/NIDA NIH HHS/United States
1R01NS067199/NS/NINDS NIH HHS/United States
1R01NS075421/NS/NINDS NIH HHS/United States
1R01NS081716/NS/NINDS NIH HHS/United States
1R01NS087950/NS/NINDS NIH HHS/United States
1R21NS078660/NS/NINDS NIH HHS/United States
1RC1MH088182/MH/NIMH NIH HHS/United States
5R00MH085944/MH/NIMH NIH HHS/United States
DP2 DK102256/DK/NIDDK NIH HHS/United States
DP2 NS082126/NS/NINDS NIH HHS/United States
DP2-OD-017366-01/OD/NIH HHS/United States
P30 ES002109/ES/NIEHS NIH HHS/United States
R00 EY018407/EY/NEI NIH HHS/United States
R01 EY022951/EY/NEI NIH HHS/United States
R01 EY022951/EY/NEI NIH HHS/United States
R01 MH091220-01/MH/NIMH NIH HHS/United States
R01 MH102365/MH/NIMH NIH HHS/United States
R01 MH102365/MH/NIMH NIH HHS/United States
R01 MH102441/MH/NIMH NIH HHS/United States
R01-MH102441-01/MH/NIMH NIH HHS/United States

CDC Public Access

Optogenetic inhibition of the electrical activity of neurons enables the causal assessment of their contributions to brain functions. Red light penetrates deeper into tissue than other visible wavelengths. We present a red-shifted cruxhalorhodopsin, Jaws, derived from Haloarcula (Halobacterium) salinarum (strain Shark) and engineered to result in red light-induced photocurrents three times those of earlier silencers. Jaws exhibits robust inhibition of sensory-evoked neural activity in the cortex and results in strong light responses when used in retinas of retinitis pigmentosa model mice. We also demonstrate that Jaws can noninvasively mediate transcranial optical inhibition of neurons deep in the brains of awake mice. The noninvasive optogenetic inhibition opened up by Jaws enables a variety of important neuroscience experiments and offers a powerful general-use chloride pump for basic and applied neuroscience.