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Multimodal fast optical interrogation of neural circuitry

Author

Listed:
  • Feng Zhang

    (Stanford University, Stanford, California 94305, USA)

  • Li-Ping Wang

    (Stanford University, Stanford, California 94305, USA)

  • Martin Brauner

    (Institute of Biochemistry, and,)

  • Jana F. Liewald

    (Institute of Biochemistry, and,)

  • Kenneth Kay

    (Stanford University, Stanford, California 94305, USA)

  • Natalie Watzke

    (Max-Planck-Institute of Biophysics, Max-von-Laue-Straβe 3, D-60438 Frankfurt am Main, Germany)

  • Phillip G. Wood

    (Max-Planck-Institute of Biophysics, Max-von-Laue-Straβe 3, D-60438 Frankfurt am Main, Germany)

  • Ernst Bamberg

    (Institute of Biophysical Chemistry, Chemistry and Pharmacy, Johann Wolfgang Goethe-University, Frankfurt Biocenter N220, Max-von-Laue Straβe 9, D-60438 Frankfurt, Germany
    Max-Planck-Institute of Biophysics, Max-von-Laue-Straβe 3, D-60438 Frankfurt am Main, Germany)

  • Georg Nagel

    (Max-Planck-Institute of Biophysics, Max-von-Laue-Straβe 3, D-60438 Frankfurt am Main, Germany
    University Wuerzburg, Botanik I, Julius-von-Sachs-Platz 2, D-97082 Wuerzburg, Germany)

  • Alexander Gottschalk

    (Institute of Biochemistry, and,)

  • Karl Deisseroth

    (Stanford University, Stanford, California 94305, USA)

Abstract

Our understanding of the cellular implementation of systems-level neural processes like action, thought and emotion has been limited by the availability of tools to interrogate specific classes of neural cells within intact, living brain tissue. Here we identify and develop an archaeal light-driven chloride pump (NpHR) from Natronomonas pharaonis for temporally precise optical inhibition of neural activity. NpHR allows either knockout of single action potentials, or sustained blockade of spiking. NpHR is compatible with ChR2, the previous optical excitation technology we have described, in that the two opposing probes operate at similar light powers but with well-separated action spectra. NpHR, like ChR2, functions in mammals without exogenous cofactors, and the two probes can be integrated with calcium imaging in mammalian brain tissue for bidirectional optical modulation and readout of neural activity. Likewise, NpHR and ChR2 can be targeted together to Caenorhabditis elegans muscle and cholinergic motor neurons to control locomotion bidirectionally. NpHR and ChR2 form a complete system for multimodal, high-speed, genetically targeted, all-optical interrogation of living neural circuits.

Suggested Citation

  • Feng Zhang & Li-Ping Wang & Martin Brauner & Jana F. Liewald & Kenneth Kay & Natalie Watzke & Phillip G. Wood & Ernst Bamberg & Georg Nagel & Alexander Gottschalk & Karl Deisseroth, 2007. "Multimodal fast optical interrogation of neural circuitry," Nature, Nature, vol. 446(7136), pages 633-639, April.
  • Handle: RePEc:nat:nature:v:446:y:2007:i:7136:d:10.1038_nature05744
    DOI: 10.1038/nature05744
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    Cited by:

    1. Stanislav Ott & Sangyu Xu & Nicole Lee & Ivan Hong & Jonathan Anns & Danesha Devini Suresh & Zhiyi Zhang & Xianyuan Zhang & Raihanah Harion & Weiying Ye & Vaishnavi Chandramouli & Suresh Jesuthasan & , 2024. "Kalium channelrhodopsins effectively inhibit neurons," Nature Communications, Nature, vol. 15(1), pages 1-21, December.
    2. Amelie C. F. Bergs & Jana F. Liewald & Silvia Rodriguez-Rozada & Qiang Liu & Christin Wirt & Artur Bessel & Nadja Zeitzschel & Hilal Durmaz & Adrianna Nozownik & Holger Dill & Maëlle Jospin & Johannes, 2023. "All-optical closed-loop voltage clamp for precise control of muscles and neurons in live animals," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    3. Dennis Vettkötter & Martin Schneider & Brady D. Goulden & Holger Dill & Jana Liewald & Sandra Zeiler & Julia Guldan & Yilmaz Arda Ateş & Shigeki Watanabe & Alexander Gottschalk, 2022. "Rapid and reversible optogenetic silencing of synaptic transmission by clustering of synaptic vesicles," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    4. Lizhu Li & Lihui Lu & Yuqi Ren & Guo Tang & Yu Zhao & Xue Cai & Zhao Shi & He Ding & Changbo Liu & Dali Cheng & Yang Xie & Huachun Wang & Xin Fu & Lan Yin & Minmin Luo & Xing Sheng, 2022. "Colocalized, bidirectional optogenetic modulations in freely behaving mice with a wireless dual-color optoelectronic probe," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    5. Daniel Bendor, 2015. "The Role of Inhibition in a Computational Model of an Auditory Cortical Neuron during the Encoding of Temporal Information," PLOS Computational Biology, Public Library of Science, vol. 11(4), pages 1-25, April.

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