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Nat Neurosci. 2017 Dec;20(12):1796-1806. doi: 10.1038/s41593-017-0018-8. Epub 2017 Nov 13.

Temporally precise single-cell-resolution optogenetics.

Shemesh OA1,2,3,4,5, Tanese D6, Zampini V6,7, Linghu C1,2,3,4,5, Piatkevich K1,2,3,4,5, Ronzitti E6,7, Papagiakoumou E6,8, Boyden ES9,10,11,12,13, Emiliani V14.

Author information

1
Media Laboratory, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA.
2
Department of Biological Engineering, MIT, Cambridge, MA, USA.
3
Center for Neurobiological Engineering, MIT, Cambridge, MA, USA.
4
Department of Brain and Cognitive Sciences, MIT, Cambridge, MA, USA.
5
McGovern Institute for Brain Research, MIT, Cambridge, MA, USA.
6
Neurophotonics Laboratory, Wave Front Engineering Microscopy Group, CNRS UMR8250, Université Paris Descartes, Paris, France.
7
Institut de la Vision, UM 80, UPMC, Paris, France.
8
Institut national de la santé et de la recherche médicale (Inserm), Paris, France.
9
Media Laboratory, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA. esb@media.mit.edu.
10
Department of Biological Engineering, MIT, Cambridge, MA, USA. esb@media.mit.edu.
11
Center for Neurobiological Engineering, MIT, Cambridge, MA, USA. esb@media.mit.edu.
12
Department of Brain and Cognitive Sciences, MIT, Cambridge, MA, USA. esb@media.mit.edu.
13
McGovern Institute for Brain Research, MIT, Cambridge, MA, USA. esb@media.mit.edu.
14
Neurophotonics Laboratory, Wave Front Engineering Microscopy Group, CNRS UMR8250, Université Paris Descartes, Paris, France. valentina.emiliani@parisdescartes.fr.

Abstract

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 photostimulation 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.

PMID:
29184208
PMCID:
PMC5726564
DOI:
10.1038/s41593-017-0018-8
[Indexed for MEDLINE]
Free PMC Article

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