Journal
NATURE NEUROSCIENCE
Volume 21, Issue 6, Pages 881-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41593-018-0139-8
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Funding
- NIH [P30 EY003176]
- New York Stem Cell Foundation
- Arnold and Mabel Beckman Foundation, NINDS [DP2NS087725-01]
- McKnight Foundation, NINDS [F32NS095690-01]
- imon's Foundation Collaboration [415569]
- David and Lucille Packard Foundation
- Defense Advanced Research Projects Agency (DARPA) [N660011-17-C-4015]
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Understanding brain function requires technologies that can control the activity of large populations of neurons with high fidelity in space and time. We developed a multiphoton holographic approach to activate or suppress the activity of ensembles of cortical neurons with cellular resolution and sub-millisecond precision. Since existing opsins were inadequate, we engineered new soma-targeted (ST) optogenetic tools, ST-ChroME and IRES-ST-eGtACR1, optimized for multiphoton activation and suppression. Employing a three-dimensional all-optical read-write interface, we demonstrate the ability to simultaneously photostimulate up to 50 neurons distributed in three dimensions in a 550 x 550 x 100-mu m(3) volume of brain tissue. This approach allows the synthesis and editing of complex neural activity patterns needed to gain insight into the principles of neural codes.
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