Magnetic stimulation allows focal activation of the mouse cochlea
Abstract
Cochlear implants (CIs) provide sound and speech sensations for patients with severe to profound hearing loss by electrically stimulating the auditory nerve. While most CI users achieve some degree of open set word recognition under quiet conditions, hearing that utilizes complex neural coding (e.g., appreciating music) has proved elusive, probably because of the inability of CIs to create narrow regions of spectral activation. Several novel approaches have recently shown promise for improving spatial selectivity, but substantial design differences from conventional CIs will necessitate much additional safety and efficacy testing before clinical viability is established. Outside the cochlea, magnetic stimulation from small coils (micro-coils) has been shown to confine activation more narrowly than that from conventional micro-electrodes, raising the possibility that coil-based stimulation of the cochlea could improve the spectral resolution of CIs. To explore this, we delivered magnetic stimulation from micro-coils to multiple locations of the cochlea and measured the spread of activation utilizing a multi-electrode array inserted into the inferior colliculus; responses to magnetic stimulation were compared to analogous experiments with conventional micro-electrodes as well as to responses when presenting auditory monotones. Encouragingly, the extent of activation with micro-coils was ~60% narrower compared to electric stimulation and largely similar to the spread arising from acoustic stimulation. The dynamic range of coils was more than three times larger than that of electrodes, further supporting a smaller spread of activation. While much additional testing is required, these results support the notion that magnetic micro-coil CIs can produce a larger number of independent spectral channels and may therefore improve auditory outcomes. Further, because coil-based devices are structurally similar to existing CIs, fewer impediments to clinical translational are likely to arise.
Data availability
The source data and codes are available on the Open Science Framework (DOI 10.17605/OSF.IO/Y7ZRX).
Article and author information
Author details
Funding
National Institutes of Health (DC 01089)
- Stephen McInturff
- Daniel J Lee
- Christian Brown
Fondation Bertarelli (Translational Neuroscience and Neuro-Engineering)
- Stephen McInturff
- Daniel J Lee
- Christian Brown
National Institute on Deafness and Other Communication Disorders (R01 DC015824)
- Richard Seist
- Konstantina M Stankovic
Fondation Bertarelli (Bertarelli Professorship)
- Richard Seist
- Konstantina M Stankovic
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All procedures were approved by the Institutional Animal Care and Use Committee of Massachusetts Eye and Ear, and carried out in accordance with the NIH Guide for the Care and Use of Laboratory Animals.(protocol# 15-003)
Copyright
This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
Metrics
-
- 1,333
- views
-
- 284
- downloads
-
- 8
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Further reading
-
- Neuroscience
By influencing calcium homeostasis, local protein synthesis and the endoplasmic reticulum, a small protein called Rab10 emerges as a crucial cytoplasmic regulator of neuropeptide secretion.
-
- Neuroscience
Millions of Americans suffering from Opioid Use Disorders face a high risk of fatal overdose due to opioid-induced respiratory depression (OIRD). Fentanyl, a powerful synthetic opioid, is a major contributor to the rising rates of overdose deaths. Reversing fentanyl overdoses has proved challenging due to its high potency and the rapid onset of OIRD. We assessed the contributions of central and peripheral mu opioid receptors (MORs) in mediating fentanyl-induced physiological responses. The peripherally restricted MOR antagonist naloxone methiodide (NLXM) both prevented and reversed OIRD to a degree comparable to that of naloxone (NLX), indicating substantial involvement of peripheral MORs to OIRD. Interestingly, NLXM-mediated OIRD reversal did not produce aversive behaviors observed after NLX. We show that neurons in the nucleus of the solitary tract (nTS), the first central synapse of peripheral afferents, exhibit a biphasic activity profile following fentanyl exposure. NLXM pretreatment attenuates this activity, suggesting that these responses are mediated by peripheral MORs. Together, these findings establish a critical role for peripheral MORs, including ascending inputs to the nTS, as sites of dysfunction during OIRD. Furthermore, selective peripheral MOR antagonism could be a promising therapeutic strategy for managing OIRD by sparing CNS-driven acute opioid-associated withdrawal and aversion observed after NLX.