Vagal determinants of exercise capacity

Asif Machhada; Stefan Trapp; Napthali Marina; Rob C. M. Stephens; Jonathan Whittle; Mark F Lythgoe; Sergey Kasparov; Gareth L. Ackland; Alexander Gourine

doi:10.1038/ncomms15097

Vagal determinants of exercise capacity

Asif Machhada, Stefan Trapp, Napthali Marina, Rob C. M. Stephens, Jonathan Whittle, Mark F Lythgoe, Sergey Kasparov, Gareth L. Ackland, Alexander Gourine

Research output: Contribution to journal › Article (Academic Journal) › peer-review

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Abstract

Indirect measures of cardiac vagal activity are strongly associated with exercise capacity, yet a causal relationship has not been established. Here we show that in rats, genetic silencing of the largest population of brainstem vagal preganglionic neurons residing in the brainstem’s dorsal vagal motor nucleus dramatically impairs exercise capacity, while optogenetic recruitment of the same neuronal population enhances cardiac contractility and prolongs exercise endurance. These data provide direct experimental evidence that arasympathetic
vagal drive generated by a defined CNS circuit determines the ability to exercise. Decreased activity and/or gradual loss of the identified neuronal cell group provides a neurophysiological basis for the progressive decline of exercise capacity with aging and in diverse disease states.

Original language	English
Article number	15097
Number of pages	7
Journal	Nature Communications
Volume	8
Early online date	18 May 2017
DOIs	https://doi.org/10.1038/ncomms15097
Publication status	Published - 18 May 2017

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28 February 2017

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Exploring astrocytic orphan G-protein coupled receptors as potential targets for neuroprotective therapies
Kasparov, S.
15/07/14 → 14/07/17
Project: Research

Professor Sergey Kasparov
- Sergey.Kasparov@bristol.ac.uk
- School of Physiology, Pharmacology & Neuroscience - Professor in Molecular Physiology
- Bristol Neuroscience
Person: Academic , Member

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title = "Vagal determinants of exercise capacity",

abstract = "Indirect measures of cardiac vagal activity are strongly associated with exercise capacity, yet a causal relationship has not been established. Here we show that in rats, genetic silencing of the largest population of brainstem vagal preganglionic neurons residing in the brainstem{\textquoteright}s dorsal vagal motor nucleus dramatically impairs exercise capacity, while optogenetic recruitment of the same neuronal population enhances cardiac contractility and prolongs exercise endurance. These data provide direct experimental evidence that arasympatheticvagal drive generated by a defined CNS circuit determines the ability to exercise. Decreased activity and/or gradual loss of the identified neuronal cell group provides a neurophysiological basis for the progressive decline of exercise capacity with aging and in diverse disease states.",

author = "Asif Machhada and Stefan Trapp and Napthali Marina and Stephens, {Rob C. M.} and Jonathan Whittle and Lythgoe, {Mark F} and Sergey Kasparov and Ackland, {Gareth L.} and Alexander Gourine",

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AU - Machhada, Asif

AU - Trapp, Stefan

AU - Marina, Napthali

AU - Stephens, Rob C. M.

AU - Whittle, Jonathan

AU - Lythgoe, Mark F

AU - Kasparov, Sergey

AU - Ackland, Gareth L.

AU - Gourine, Alexander

N1 - 28 February 2017

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N2 - Indirect measures of cardiac vagal activity are strongly associated with exercise capacity, yet a causal relationship has not been established. Here we show that in rats, genetic silencing of the largest population of brainstem vagal preganglionic neurons residing in the brainstem’s dorsal vagal motor nucleus dramatically impairs exercise capacity, while optogenetic recruitment of the same neuronal population enhances cardiac contractility and prolongs exercise endurance. These data provide direct experimental evidence that arasympatheticvagal drive generated by a defined CNS circuit determines the ability to exercise. Decreased activity and/or gradual loss of the identified neuronal cell group provides a neurophysiological basis for the progressive decline of exercise capacity with aging and in diverse disease states.

AB - Indirect measures of cardiac vagal activity are strongly associated with exercise capacity, yet a causal relationship has not been established. Here we show that in rats, genetic silencing of the largest population of brainstem vagal preganglionic neurons residing in the brainstem’s dorsal vagal motor nucleus dramatically impairs exercise capacity, while optogenetic recruitment of the same neuronal population enhances cardiac contractility and prolongs exercise endurance. These data provide direct experimental evidence that arasympatheticvagal drive generated by a defined CNS circuit determines the ability to exercise. Decreased activity and/or gradual loss of the identified neuronal cell group provides a neurophysiological basis for the progressive decline of exercise capacity with aging and in diverse disease states.

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DO - 10.1038/ncomms15097

M3 - Article (Academic Journal)

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VL - 8

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

M1 - 15097

ER -

Vagal determinants of exercise capacity

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Projects

Exploring astrocytic orphan G-protein coupled receptors as potential targets for neuroprotective therapies

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Professor Sergey Kasparov

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