Glial responses to implanted electrodes in the brain

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.

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

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Correspondence to Erin K. Purcell.

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A correction to this article is available online at https://doi.org/10.1038/s41551-017-0177-7.

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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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