Temporally precise single-cell resolution optogenetics

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Or A. Shemesh*, Dimitrii Tanese*, Valeria Zampini*, Changyang Linghu, Kiryl Piatkevich, Emiliano Ronzitti, Eirini Papagiakoumou, Edward S. Boyden+ and Valentina Emiliani+ (2017) Temporally precise single-cell resolution optogenetics, Nature Neuroscience 20:1796–1806. (*, co-first authors; +, co-corresponding authors)

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.

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