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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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.
The authors declare no competing financial interests.
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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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