Temporally precise single-cell resolution optogenetics

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. The authors develop a methods suite for millisecond-precise, single-cell-resolution control of neural activity through protein engineering of novel opsin/trafficking sequence combinations, as well as optimized holographic two-photon optics.

• Publication year

  2017

• Venue

  Nature Neuroscience

• Publication date

  2017-09-29

• Fields of study

  Medicine, Physics, Engineering

• Identifiers
  DOI 10.1038/s41593-017-0018-8PMID 29184208PMCID 5726564
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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