Combined-electrical optogenetic stimulation but not channelrhodopsin kinetics improves the fidelity of high rate stimulation in the auditory pathway in mice

• Published in: Scientific reports Vol. 14; no. 1; pp. 21028 - 18
• Main Authors: Ajay, Elise A., Thompson, Alex C., Azees, Ajmal A., Wise, Andrew K., Grayden, David B., Fallon, James B., Richardson, Rachael T.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 09.09.2024; Nature Publishing Group; Nature Portfolio
• Subjects: 631/378; 631/378/2619; Animals; Auditory nerve; Auditory Pathways - metabolism; Auditory Pathways - physiology; Biomedical engineering; Channelrhodopsins - genetics; Channelrhodopsins - metabolism; Cochlea; Cochlear Implants; Cochlear Nerve - metabolism; Cochlear Nerve - physiology; Electric Stimulation - methods; Electrical stimuli; Electrodes; Fidelity; Genetics; Hearing loss; Hearing protection; Humanities and Social Sciences; Inferior Colliculi - metabolism; Inferior Colliculi - physiology; Inferior colliculus; Information processing; Ion channels; Kinetics; Latency; Light; Mice; multidisciplinary; Mutation; Opsins; Optics; Optogenetics - methods; Science; Science (multidisciplinary); Translation; Transplants & implants
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-024-71712-9

Novel stimulation methods are needed to overcome the limitations of contemporary cochlear implants. Optogenetics is a technique that confers light sensitivity to neurons via the genetic introduction of light-sensitive ion channels. By controlling neural activity with light, auditory neurons can be activated with higher spatial precision. Understanding the behaviour of opsins at high stimulation rates is an important step towards their translation. To elucidate this, we compared the temporal characteristics of auditory nerve and inferior colliculus responses to optogenetic, electrical, and combined optogenetic-electrical stimulation in virally transduced mice expressing one of two channelrhodopsins, ChR2-H134R or ChIEF, at stimulation rates up to 400 pulses per second (pps). At 100 pps, optogenetic responses in ChIEF mice demonstrated higher fidelity, less change in latency, and greater response stability compared to responses in ChR2-H134R mice, but not at higher rates. Combined stimulation improved the response characteristics in both cohorts at 400 pps, although there was no consistent facilitation of electrical responses. Despite these results, day-long stimulation (up to 13 h) led to severe and non-recoverable deterioration of the optogenetic responses. The results of this study have significant implications for the translation of optogenetic-only and combined stimulation techniques for hearing loss.