Multimodal fast optical interrogation of neural circuitry

Feng Zhang, Li-Ping Wang, Martin Brauner, Jana F. Liewald, Kenneth Kay, Natalie Watzke, Phillip G. Wood, Ernst Bamberg, Georg Nagel, Alexander Gottschalk and Karl Deisseroth ()
Additional contact information
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
Georg Nagel: Max-Planck-Institute of Biophysics, Max-von-Laue-Straβe 3, D-60438 Frankfurt am Main, Germany
Alexander Gottschalk: Institute of Biochemistry, and,
Karl Deisseroth: Stanford University, Stanford, California 94305, USA

Nature, 2007, vol. 446, issue 7136, 633-639

Abstract: 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.

Date: 2007
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DOI: 10.1038/nature05744

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