Selective optogenetic stimulation of efferent fi bers in the vagus nerve of a large mammal
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Volume
14
Pagination
88 - 96
Publisher
DOI
10.1016/j.brs.2020.11.010
Journal
BRAIN STIMULATION
Issue
ISSN
1935-861X
Metadata
Show full item recordAbstract
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 optogenetic technology for
autonomic neuromodulation.
© 2020 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license
(http://creativecommons.org/licenses/by/4.0/)