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Selective optogenetic stimulation of efferent fibers in the vagus nerve of a large mammal.
Booth, Lindsea C; Yao, Song T; Korsak, Alla; Farmer, David G S; Hood, Sally G; McCormick, Daniel; Boesley, Quinn; Connelly, Angela A; McDougall, Stuart J; Korim, Willian S; Guild, Sarah-Jane; Mastitskaya, Svetlana; Le, Phuong; Teschemacher, Anja G; Kasparov, Sergey; Ackland, Gareth L; Malpas, Simon C; McAllen, Robin M; Allen, Andrew M; May, Clive N; Gourine, Alexander V.
Afiliación
  • Booth LC; Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne, Australia.
  • Yao ST; Florey Department of Neuroscience and Mental Health, MDHS, University of Melbourne, Melbourne, Australia.
  • Korsak A; Centre for Cardiovascular and Metabolic Neuroscience, Department of Neuroscience, Physiology and Pharmacology, University College London, London, UK.
  • Farmer DGS; Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne, Australia; Department of Physiology, The University of Melbourne, Melbourne, Australia.
  • Hood SG; Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne, Australia.
  • McCormick D; Department of Physiology and Auckland Bioengineering Institute, University of Auckland, Auckland, New Zealand.
  • Boesley Q; Department of Physiology and Auckland Bioengineering Institute, University of Auckland, Auckland, New Zealand.
  • Connelly AA; Department of Physiology, The University of Melbourne, Melbourne, Australia.
  • McDougall SJ; Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne, Australia.
  • Korim WS; Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne, Australia.
  • Guild SJ; Department of Physiology and Auckland Bioengineering Institute, University of Auckland, Auckland, New Zealand.
  • Mastitskaya S; Centre for Cardiovascular and Metabolic Neuroscience, Department of Neuroscience, Physiology and Pharmacology, University College London, London, UK.
  • Le P; Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne, Australia.
  • Teschemacher AG; Physiology, Neuroscience and Pharmacology, University of Bristol, Bristol, UK.
  • Kasparov S; Physiology, Neuroscience and Pharmacology, University of Bristol, Bristol, UK; Baltic Federal University, Kaliningrad, Russian Federation.
  • Ackland GL; Translational Medicine and Therapeutics, William Harvey Research Institute, Queen Mary University of London, London, UK.
  • Malpas SC; Department of Physiology and Auckland Bioengineering Institute, University of Auckland, Auckland, New Zealand.
  • McAllen RM; Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne, Australia.
  • Allen AM; Department of Physiology, The University of Melbourne, Melbourne, Australia.
  • May CN; Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne, Australia. Electronic address: clive.may@florey.edu.au.
  • Gourine AV; Centre for Cardiovascular and Metabolic Neuroscience, Department of Neuroscience, Physiology and Pharmacology, University College London, London, UK. Electronic address: a.gourine@ucl.ac.uk.
Brain Stimul ; 14(1): 88-96, 2021.
Article en En | MEDLINE | ID: mdl-33217609
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Estimulación del Nervio Vago / Optogenética Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Brain Stimul Asunto de la revista: CEREBRO Año: 2021 Tipo del documento: Article País de afiliación: Australia Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Estimulación del Nervio Vago / Optogenética Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Brain Stimul Asunto de la revista: CEREBRO Año: 2021 Tipo del documento: Article País de afiliación: Australia Pais de publicación: Estados Unidos