Journal
NATURE NEUROSCIENCE
Volume 20, Issue 12, Pages 1796-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41593-017-0018-8
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Funding
- Agence Nationale de la Recherche (France-BioImaging Infrastructure network) [ANR-10-INBS-04-01]
- Agence Nationale de la Recherche (Holohub) [ANR-14-CE13-0016]
- National Institutes of Health [NIH 1-U01-NS090501-01]
- FRC
- Rotary Club
- Getty Lab
- Simons Foundation
- ISEF (International Sephardic Educational Foundation)
- Defense Advanced Research Projects Agency (DARPA) [N66001-17-C-4015]
- Human Frontiers Science Program [RGP0015/2016]
- Open Philanthropy Project
- HHMI-Simons Faculty Scholars Program, NIH [R44EB021054]
- MIT Media Lab [NIH 1R24MH106075, NIH 2R01DA029639, NIH 1R01NS087950, NIH 1R01MH103910]
- NIH [1DP1NS087724, 1R01GM104948]
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Optogenetic control of individual neurons with high temporal precision within intact mammalian brain circuitry would enable powerful explorations of how neural circuits operate. Two-photon computer-generated holography enables precise sculpting of light and could in principle enable simultaneous illumination of many neurons in a network, with the requisite temporal precision to simulate accurate neural codes. We designed a high-efficacy soma-targeted opsin, finding that fusing the N-terminal 150 residues of kainate receptor subunit 2 (KA2) to the recently discovered high-photocurrent channelrhodopsin CoChR restricted expression of this opsin primarily to the cell body of mammalian cortical neurons. In combination with two-photon holographic stimulation, we found that this somatic CoChR (soCoChR) enabled photo-stimulation of individual cells in mouse cortical brain slices with single-cell resolution and <1-ms temporal precision. We used soCoChR to perform connectivity mapping on intact cortical circuits.
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