Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Protocol
  • Published:

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

Nature Protocols volume 7, pages 12–23 (2012)Cite this article

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.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

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.

Similar content being viewed by others

References

  1. Claridge-Chang, A. et al. Writing memories with light-addressable reinforcement circuitry. Cell 139, 405–415 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Guo, Z.V., Hart, A.C. & Ramanathan, S. Optical interrogation of neural circuits in Caenorhabditis elegans. Nat. Methods 6, 891–896 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Liewald, J.F. et al. Optogenetic analysis of synaptic function. Nat. Methods 5, 895–902 (2008).

    Article  CAS  PubMed  Google Scholar 

  4. Zhu, P. et al. Optogenetic dissection of neuronal circuits in zebrafish using viral gene transfer and the Tet system. Front. Neural Circuits 3, 21 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  5. Tsai, H.C. et al. Phasic firing in dopaminergic neurons is sufficient for behavioral conditioning. Science (New York, NY) 324, 1080–1084 (2009).

    Article  CAS  Google Scholar 

  6. Adamantidis, A.R., Zhang, F., Aravanis, A.M., Deisseroth, K. & de Lecea, L. Neural substrates of awakening probed with optogenetic control of hypocretin neurons. Nature 450, 420–424 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Kravitz, A.V. et al. Regulation of parkinsonian motor behaviours by optogenetic control of basal ganglia circuitry. Nature 466, 622–626 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Tye, K.M. et al. Amygdala circuitry mediating reversible and bidirectional control of anxiety. Nature 471, 358–362 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Lin, D. et al. Functional identification of an aggression locus in the mouse hypothalamus. Nature 470, 221–226 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Witten, I.B. et al. Cholinergic interneurons control local circuit activity and cocaine conditioning. Science (New York, NY) 330, 1677–1681 (2010).

    Article  CAS  Google Scholar 

  11. Zhang, F. et al. Optogenetic interrogation of neural circuits: technology for probing mammalian brain structures. Nat. Protoc. 5, 439–456 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Covington, H.E., III et al. Antidepressant effect of optogenetic stimulation of the medial prefrontal cortex. J. Neurosci. 30, 16082–16090 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Han, X. et al. Millisecond-timescale optical control of neural dynamics in the nonhuman primate brain. Neuron 62, 191–198 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Diester, I. et al. An optogenetic toolbox designed for primates. Nat. Neurosci. 14, 387–397 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Stuber, G.D. et al. Amygdala to nucleus accumbens excitatory transmission facilitates reward seeking. Nature 475, 377–380 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Cardin, J.A. et al. Driving fast-spiking cells induces gamma rhythm and controls sensory responses. Nature 459, 663–667 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Kravitz, A.V. & Kreitzer, A.C. Optogenetic manipulation of neural circuitry in vivo. Curr. Opin. Neurobiol. 21, 433–439 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Martin-Garcia, E. et al. New operant model of reinstatement of food-seeking behavior in mice. Psychopharmacology 215, 49–70 (2010).

    Article  PubMed  Google Scholar 

  19. Olsen, C.M. & Winder, D.G. Operant sensation seeking engages similar neural substrates to operant drug seeking in C57 mice. Neuropsychopharmacology 34, 1685–1694 (2009).

    Article  CAS  PubMed  Google Scholar 

  20. Aravanis, A.M. et al. An optical neural interface: in vivo control of rodent motor cortex with integrated fiberoptic and optogenetic technology. J. Neural Eng. 4, S143–S156 (2007).

    Article  PubMed  Google Scholar 

  21. Tian, L. et al. Imaging neural activity in worms, flies and mice with improved GCaMP calcium indicators. Nat. Methods 6, 875–881 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Cardin, J.A. et al. Targeted optogenetic stimulation and recording of neurons in vivo using cell-type-specific expression of Channelrhodopsin-2. Nat. Protoc. 5, 247–254 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

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.).

Author information

Authors and Affiliations

  1. Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA

    Dennis R Sparta, Alice M Stamatakis, Jana L Phillips, Nanna Hovelsø, Ruud van Zessen & Garret D Stuber

  2. Department of Cell and Molecular Physiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA

    Dennis R Sparta, Alice M Stamatakis, Jana L Phillips, Ruud van Zessen & Garret D Stuber

  3. Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA

    Dennis R Sparta, Alice M Stamatakis, Jana L Phillips, Ruud van Zessen & Garret D Stuber

  4. Curriculum in Neurobiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA

    Alice M Stamatakis & Garret D Stuber

  5. Synaptic Transmission 1, Neuroscience Drug Discovery Denmark, H. Lundbeck, Copenhagen-Valby, Denmark

    Nanna Hovelsø

  6. Department of Neuroscience and Pharmacology, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark

    Nanna Hovelsø

Authors
  1. Dennis R Sparta
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Alice M Stamatakis
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jana L Phillips
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Nanna Hovelsø
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ruud van Zessen
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Garret D Stuber
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

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.

Corresponding author

Correspondence to Garret D Stuber.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Cite this article

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

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nprot.2011.413

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing