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  • Review Article
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Glial responses to implanted electrodes in the brain

Nature Biomedical Engineering volume 1, pages 862–877 (2017)Cite this article

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A Publisher Correction to this article was published on 07 December 2017

This article has been updated

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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Fig. 1: Traditional electrode arrays incite gliosis.
Fig. 2: In vivo multiphoton imaging of the glial response to the implantation of a multielectrode array.
Fig. 3: Evidence for a negative impact of increased gliosis on recording quality.
Fig. 4: Potential mechanisms of the active modulation of neurotransmission by glia.
Fig. 5: Next-generation arrays mitigate gliosis.
Fig. 6: Opportunities for further enquiry in device design.
Fig. 7: Opportunities for further biological enquiry.

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Change history

  • 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.

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Authors and 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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Salatino, J.W., Ludwig, K.A., Kozai, T.D.Y. et al. Glial responses to implanted electrodes in the brain. Nat Biomed Eng 1, 862–877 (2017). https://doi.org/10.1038/s41551-017-0154-1

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