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Optical Deconstruction of Parkinsonian Neural Circuitry

Gradinaru, Viviana and Mogri, Murtaza and Thompson, Kimberly R. and Henderson, Jaimie M. and Deisseroth, Karl (2009) Optical Deconstruction of Parkinsonian Neural Circuitry. Science, 324 (5925). pp. 354-359. ISSN 0036-8075. http://resolver.caltech.edu/CaltechAUTHORS:20121211-083527990

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Abstract

Deep brain stimulation (DBS) is a therapeutic option for intractable neurological and psychiatric disorders, including Parkinson's disease and major depression. Because of the heterogeneity of brain tissues where electrodes are placed, it has been challenging to elucidate the relevant target cell types or underlying mechanisms of DBS. We used optogenetics and solid-state optics to systematically drive or inhibit an array of distinct circuit elements in freely moving parkinsonian rodents and found that therapeutic effects within the subthalamic nucleus can be accounted for by direct selective stimulation of afferent axons projecting to this region. In addition to providing insight into DBS mechanisms, these results demonstrate an optical approach for dissection of disease circuitry and define the technological toolbox needed for systematic deconstruction of disease circuits by selectively controlling individual components.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1126/science.1167093 DOIArticle
http://www.sciencemag.org/content/324/5925/354PublisherArticle
ORCID:
AuthorORCID
Gradinaru, Viviana0000-0001-5868-348X
Additional Information:© 2009 American Association for the Advancement of Science. Received for publication 13 October 2008. Accepted for publication 20 February 2009. K.D. is supported by the Kinetics Foundation, 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. V.G. is supported by SGF and SIGF (Stanford Graduate Fellowships). M.M is supported by Bio-X and SGF Fellowships. K.R.T. is supported by NARSAD. J.M.H is supported by the Coulter Foundation, the John Blume Foundation and the Davis Phinney Foundation. We especially thank A. M. Aravanis for mentoring and advice on animal surgery and in vivo recordings, F. Zhang and H. C. Tsai for assistance with Cre-dependent opsin targeting, L. Meltzer for useful discussion, advice and help on immunohistochemistry, G. Feng and G. Augustine for collaboration on generation of the Thy-1 mice (available at the Jackson Laboratory), and V. Sohal for help with power spectra analysis. We also thank the entire Deisseroth lab for useful discussions. The materials and methods described herein are freely distributed and supported by the authors (www.stanford.edu/group/dlab).
Funders:
Funding AgencyGrant Number
Kinetics FoundationUNSPECIFIED
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
NSFUNSPECIFIED
National Institute of Mental Health (NIMH)UNSPECIFIED
National Institute on Drug AbuseUNSPECIFIED
NIHUNSPECIFIED
Stanford Graduate FellowshipUNSPECIFIED
Stanford Interdisciplinary Graduate Fellowship ProgramUNSPECIFIED
Bio-X FellowshipUNSPECIFIED
NARSADUNSPECIFIED
John Blume FoundationUNSPECIFIED
Davis Phinney FoundationUNSPECIFIED
Record Number:CaltechAUTHORS:20121211-083527990
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:20121211-083527990
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:35900
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:12 Dec 2012 22:46
Last Modified:22 Nov 2016 20:39

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