Selective optogenetic stimulation of efferent fibers in the vagus nerve of a large mammal.
Abstract
BACKGROUND: Electrical stimulation applied to individual organs, peripheral nerves, or specific brain regions has been used to treat a range of medical conditions. In cardiovascular disease, autonomic dysfunction contributes to the disease progression and electrical stimulation of the vagus nerve has been pursued as a treatment for the purpose of restoring the autonomic balance. However, this approach lacks selectivity in activating function- and organ-specific vagal fibers and, despite promising results of many preclinical studies, has so far failed to translate into a clinical treatment of cardiovascular disease.
OBJECTIVE: Here we report a successful application of optogenetics for selective stimulation of vagal efferent activity in a large animal model (sheep).
METHODS AND RESULTS: Twelve weeks after viral transduction of a subset of vagal motoneurons, strong axonal membrane expression of the excitatory light-sensitive ion channel ChIEF was achieved in the efferent projections innervating thoracic organs and reaching beyond the level of the diaphragm. Blue laser or LED light (>10 mW mm-2; 1 ms pulses) applied to the cervical vagus triggered precisely timed, strong bursts of efferent activity with evoked action potentials propagating at speeds of ∼6 m s-1.
CONCLUSIONS: These findings demonstrate that in species with a large, multi-fascicled vagus nerve, it is possible to stimulate a specific sub-population of efferent fibers using light at a site remote from the vector delivery, marking an important step towards eventual clinical use of the optogenetic technology for autonomic neuromodulation.
PMID: 33217609 [PubMed – as supplied by publisher]
Brain Stimul. 2020 Nov 17;:
Authors: Booth LC, Yao ST, Korsak A, Farmer DGS, Hood SG, McCormick D, Boesley Q, Connelly AA, McDougall SJ, Korim WS, Guild SJ, Mastitskaya S, Le P, Teschemacher AG, Kasparov S, Ackland GL, Malpas SC, McAllen RM, Allen AM, May CN, Gourine AV
