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Construction of implantable optical fibers for long-term optogenetic manipulation of neural circuits

Abstract

In vivo optogenetic strategies have redefined our ability to assay how neural circuits govern behavior. Although acutely implanted optical fibers have previously been used in such studies, long-term control over neuronal activity has been largely unachievable. Here we describe a method to construct implantable optical fibers to readily manipulate neural circuit elements with minimal tissue damage or change in light output over time (weeks to months). Implanted optical fibers readily interface with in vivo electrophysiological arrays or electrochemical detection electrodes. The procedure described here, from implant construction to the start of behavioral experimentation, can be completed in approximately 2–6 weeks. Successful use of implantable optical fibers will allow for long-term control of mammalian neural circuits in vivo, which is integral to the study of the neurobiology of behavior.

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Figure 1: Light transmission from implantable optical fibers before and after implantation.
Figure 2: Construction of implantable optical fibers.
Figure 3: Construction of patch cables for use in in vivo optogenetic experiments.
Figure 4: Interfacing implantable optical fibers with in vivo electrophysiological arrays.
Figure 5: Implantation of optical fibers.

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Acknowledgements

We thank A. Kravitz, M. Patel, J. Smithius, M. Weber and D. Albaugh for discussion and assistance. This study was supported by funds from the National Institute on Alcohol Abuse and Alcoholism (NIAA) (F32AA018610 to D.R.S.), the National Alliance for Research on Schizophrenia and Depression (NARSAD), The Whitehall Foundation, the Foundation for Alcohol Research (ABMRF), the Foundation of Hope, the National Institute on Drug Abuse (DA029325) and startup funds provided by the Department of Psychiatry at the University of North Carolina at Chapel Hill (G.D.S.).

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D.R.S., A.M.S., J.L.P., N.H., R.v.Z. and G.D.S. performed the experiments. D.R.S., A.M.S., J.L.P., N.H. and G.D.S. developed the protocol. D.R.S. and G.D.S wrote the manuscript.

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Correspondence to Garret D Stuber.

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The authors declare no competing financial interests.

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Sparta, D., Stamatakis, A., Phillips, J. et al. Construction of implantable optical fibers for long-term optogenetic manipulation of neural circuits. Nat Protoc 7, 12–23 (2012). https://doi.org/10.1038/nprot.2011.413

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