Browsing by Author "Thompson, Alex C"

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    Combined optogenetic and electrical stimulation of the sciatic nerve for selective control of sensory fibers.
    (Frontiers in Neuroscience, 2023-06-08) Matarazzo, Jerico V; Ajay, Elise A; Payne, Sophie C; Trang, Ella P; Thompson, Alex C; Marroquin, Jason B; Wise, Andrew K; Fallon, James B; Richardson, Rachael T
    Electrical stimulation offers a drug-free alternative for the treatment of many neurological conditions, such as chronic pain. However, it is not easy to selectively activate afferent or efferent fibers of mixed nerves, nor their functional subtypes. Optogenetics overcomes these issues by controlling activity selectively in genetically modified fibers, however the reliability of responses to light are poor compared to electrical stimulation and the high intensities of light required present considerable translational challenges. In this study we employed a combined protocol of optical and electrical stimulation to the sciatic nerve in an optogenetic mouse model to allow for better selectivity, efficiency, and safety to overcome fundamental limitations of electrical-only and optical-only stimulation.
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    Combined-electrical optogenetic stimulation but not channelrhodopsin kinetics improves the fidelity of high rate stimulation in the auditory pathway in mice.
    (Scientific Reports, 2024-09-09) Ajay, Elise A; Thompson, Alex C; Azees, Ajmal A; Wise, Andrew K; Grayden, David B; Fallon, James B; Richardson, Rachael T
    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.