Review Article

Glial responses to implanted electrodes in the brain

  • Nature Biomedical Engineering 1862877 (2017)
  • doi:10.1038/s41551-017-0154-1
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Abstract

The use of implants that can electrically stimulate or record electrophysiological or neurochemical activity in nervous tissue is rapidly expanding. Despite remarkable results in clinical studies and increasing market approvals, the mechanisms underlying the therapeutic effects of neuroprosthetic and neuromodulation devices, as well as their side effects and reasons for their failure, remain poorly understood. A major assumption has been that the signal-generating neurons are the only important target cells of neural-interface technologies. However, recent evidence indicates that the supporting glial cells remodel the structure and function of neuronal networks and are an effector of stimulation-based therapy. Here, we reframe the traditional view of glia as a passive barrier, and discuss their role as an active determinant of the outcomes of device implantation. We also discuss the implications that this has on the development of bioelectronic medical devices.

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Change history

  • Correction 07 December 2017

    In the version of this Review Article originally published, in Fig. 4b, the label ‘Glutamate’ was mistakenly duplicated and an arrow between a purinergic P2 receptor and a glutamate transporter was missing. The figure has now been updated in all versions of the Review Article.

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Acknowledgements

J.W.S. was supported by National Institutes of Health (NIH) 1R21NS094900, T.D.Y.K. was supported by NIH 1R01NS094396, K.A.L. was supported by The Grainger Foundation, and E.K.P. was supported by NIH 1R21NS094900 and 5R03NS095202. The authors thank J. Eles for assistance collecting in vivo imaging data (Fig. 2a), D. Thompson and S. Yandamuri for assistance collecting data presented in Fig. 3, and M.-C. Senut of Biomilab, LLC, for providing feedback.

Author information

Affiliations

  1. Department of Biomedical Engineering, Michigan State University, East Lansing, MI, USA

    • Joseph W. Salatino
    •  & Erin K. Purcell
  2. Institute for Quantitative Health Science and Engineering, Michigan State University, East Lansing, MI, USA

    • Joseph W. Salatino
    •  & Erin K. Purcell
  3. Department of Neurologic Surgery, Mayo Clinic, Rochester, MN, USA

    • Kip A. Ludwig
  4. Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA

    • Takashi D. Y. Kozai
  5. Center for the Neural Basis of Cognition, University of Pittsburgh, Pittsburgh, PA, USA

    • Takashi D. Y. Kozai
  6. McGowan Institute of Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA, USA

    • Takashi D. Y. Kozai
  7. Neurotech Center, University of Pittsburgh Brain Institute, Pittsburgh, PA, USA

    • Takashi D. Y. Kozai
  8. Department of Electrical and Computer Engineering, Michigan State University, East Lansing, MI, USA

    • Erin K. Purcell
  9. Neuroscience Program, Michigan State University, East Lansing, MI, USA

    • Erin K. Purcell

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Contributions

All authors contributed to researching the data and discussing the content of the manuscript, and to writing, reviewing and editing it.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Erin K. Purcell.