Journal
BRAIN STIMULATION
Volume 14, Issue 1, Pages 88-96Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.brs.2020.11.010
Keywords
Autonomic nervous system; Brainstem; Neuromodulation; Optogenetic; Vagal preganglionic neurons; Vagus nerve stimulation
Categories
Funding
- British Heart Foundation [RG/14/4/30736, RG/19/5/34463]
- Medical Research Council [MR/R01213X/1]
- Hugo Charitable Trust
- NHMRC [1128108]
- 5-100 programme
- BBSRC [BB/L019396/1] Funding Source: UKRI
- MRC [MR/R01213X/1] Funding Source: UKRI
- National Health and Medical Research Council of Australia [1128108] Funding Source: NHMRC
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This study successfully applied optogenetics for selective stimulation of vagal efferent activity in a large animal model (sheep). Viral transduction of a subset of vagal motoneurons resulted in strong axonal membrane expression of the excitatory light-sensitive ion channel ChIEF in efferent projections innervating thoracic organs and reaching beyond the diaphragm.
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 functionand 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 similar to 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 optogenetic technology for autonomic neuromodulation. (C) 2020 The Author(s). Published by Elsevier Inc.
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