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Optogenetic interrogation of neural circuits: technology for probing mammalian brain structures

Zhang, Feng and Gradinaru, Viviana and Adamantidis, Antoine R. and Durand, Remy and Airan, Raag D. and de Lecea, Luis and Deisseroth, Karl (2010) Optogenetic interrogation of neural circuits: technology for probing mammalian brain structures. Nature Protocols, 5 (3). pp. 439-456. ISSN 1754-2189. PMCID PMC4503465.

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Elucidation of the neural substrates underlying complex animal behaviors depends on precise activity control tools, as well as compatible readout methods. Recent developments in optogenetics have addressed this need, opening up new possibilities for systems neuroscience. Interrogation of even deep neural circuits can be conducted by directly probing the necessity and sufficiency of defined circuit elements with millisecond-scale, cell type-specific optical perturbations, coupled with suitable readouts such as electrophysiology, optical circuit dynamics measures and freely moving behavior in mammals. Here we collect in detail our strategies for delivering microbial opsin genes to deep mammalian brain structures in vivo, along with protocols for integrating the resulting optical control with compatible readouts (electrophysiological, optical and behavioral). The procedures described here, from initial virus preparation to systems-level functional readout, can be completed within 4–5 weeks. Together, these methods may help in providing circuit-level insight into the dynamics underlying complex mammalian behaviors in health and disease.

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Gradinaru, Viviana0000-0001-5868-348X
Additional Information:© 2010 Nature Publishing Group. Published online: 18 February 2010. We thank the entire Deisseroth laboratory for their support. F.Z. is supported by an NIH NRSA. V.G. is supported by SGF and SIGF (Stanford Graduate Fellowships). A.R.A. is supported by the Fonds National de la Recherche Scientifique, NARSAD, NIH (K99) and the Fondation Leon Fredericq. L.d.L. is supported by NIDA, DARPA and NARSAD. K.D. is supported by the William M. Keck Foundation, the Snyder Foundation, the Albert Yu and Mary Bechmann Foundation and the Wallace Coulter Foundation, as well as by California Institute for Regenerative Medicine, the McKnight Foundation, the Esther A. and Joseph Klingenstein Fund, NSF, National Institute of Mental Health, National Institute on Drug Abuse and the NIH Pioneer Award. Author Contributions: F.Z., V.G., A.R.A., R.D.A., R.D., L.d.L. and K.D. wrote the manuscript.
Funding AgencyGrant Number
NIH Predoctoral FellowshipUNSPECIFIED
Stanford Graduate FellowshipUNSPECIFIED
Stanford Interdisciplinary Graduate Fellowship ProgramUNSPECIFIED
Fonds de la Recherche Scientifique (FNRS)UNSPECIFIED
Fondation Leon FredericqUNSPECIFIED
National Institute on Drug AbuseUNSPECIFIED
Defense Advanced Research Projects Agency (DARPA)UNSPECIFIED
W. M. Keck FoundationUNSPECIFIED
H. L. Snyder Medical FoundationUNSPECIFIED
Albert Yu and Mary Bechmann FoundationUNSPECIFIED
Wallace Coulter FoundationUNSPECIFIED
California Institute for Regenerative Medicine (CIRM)UNSPECIFIED
McKnight FoundationUNSPECIFIED
Esther A. and Joseph Klingenstein FundUNSPECIFIED
National Institute of Mental Health (NIMH)UNSPECIFIED
Subject Keywords:Imaging; Model organisms; Neuroscience
Issue or Number:3
PubMed Central ID:PMC4503465
Record Number:CaltechAUTHORS:20121206-154946294
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Official Citation:Optogenetic interrogation of neural circuits: technology for probing mammalian brain structures Feng Zhang, Viviana Gradinaru, Antoine R Adamantidis, Remy Durand, Raag D Airan, Luis de Lecea & Karl Deisseroth Nature Protocols 5, - 439 - 456 (2010)
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:35864
Deposited By: Tony Diaz
Deposited On:07 Dec 2012 18:06
Last Modified:14 Apr 2020 17:55

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