Optical vagus nerve modulation of heart and respiration via heart-injected retrograde AAV

Abstract Vagus nerve stimulation has shown many benefits for disease therapies but current approaches involve imprecise electrical stimulation that gives rise to off-target effects, while the functionally relevant pathways remain poorly understood. One method to overcome these limitations is the use...

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Autores principales:	Arjun K. Fontaine, Gregory L. Futia, Pradeep S. Rajendran, Samuel F. Littich, Naoko Mizoguchi, Kalyanam Shivkumar, Jeffrey L. Ardell, Diego Restrepo, John H. Caldwell, Emily A. Gibson, Richard F. ff Weir
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e5554b021ce340498706e2698c75bcce
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spelling	oai:doaj.org-article:e5554b021ce340498706e2698c75bcce2021-12-02T14:11:29ZOptical vagus nerve modulation of heart and respiration via heart-injected retrograde AAV10.1038/s41598-021-83280-32045-2322https://doaj.org/article/e5554b021ce340498706e2698c75bcce2021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-83280-3https://doaj.org/toc/2045-2322Abstract Vagus nerve stimulation has shown many benefits for disease therapies but current approaches involve imprecise electrical stimulation that gives rise to off-target effects, while the functionally relevant pathways remain poorly understood. One method to overcome these limitations is the use of optogenetic techniques, which facilitate targeted neural communication with light-sensitive actuators (opsins) and can be targeted to organs of interest based on the location of viral delivery. Here, we tested whether retrograde adeno-associated virus (rAAV2-retro) injected in the heart can be used to selectively express opsins in vagus nerve fibers controlling cardiac function. Furthermore, we investigated whether perturbations in cardiac function could be achieved with photostimulation at the cervical vagus nerve. Viral injection in the heart resulted in robust, primarily afferent, opsin reporter expression in the vagus nerve, nodose ganglion, and brainstem. Photostimulation using both one-photon stimulation and two-photon holography with a GRIN-lens incorporated nerve cuff, was tested on the pilot-cohort of injected mice. Changes in heart rate, surface electrocardiogram, and respiratory responses were observed in response to both one- and two-photon photostimulation. The results demonstrate feasibility of retrograde labeling for organ targeted optical neuromodulation.Arjun K. FontaineGregory L. FutiaPradeep S. RajendranSamuel F. LittichNaoko MizoguchiKalyanam ShivkumarJeffrey L. ArdellDiego RestrepoJohn H. CaldwellEmily A. GibsonRichard F. ff WeirNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Arjun K. Fontaine Gregory L. Futia Pradeep S. Rajendran Samuel F. Littich Naoko Mizoguchi Kalyanam Shivkumar Jeffrey L. Ardell Diego Restrepo John H. Caldwell Emily A. Gibson Richard F. ff Weir Optical vagus nerve modulation of heart and respiration via heart-injected retrograde AAV
description	Abstract Vagus nerve stimulation has shown many benefits for disease therapies but current approaches involve imprecise electrical stimulation that gives rise to off-target effects, while the functionally relevant pathways remain poorly understood. One method to overcome these limitations is the use of optogenetic techniques, which facilitate targeted neural communication with light-sensitive actuators (opsins) and can be targeted to organs of interest based on the location of viral delivery. Here, we tested whether retrograde adeno-associated virus (rAAV2-retro) injected in the heart can be used to selectively express opsins in vagus nerve fibers controlling cardiac function. Furthermore, we investigated whether perturbations in cardiac function could be achieved with photostimulation at the cervical vagus nerve. Viral injection in the heart resulted in robust, primarily afferent, opsin reporter expression in the vagus nerve, nodose ganglion, and brainstem. Photostimulation using both one-photon stimulation and two-photon holography with a GRIN-lens incorporated nerve cuff, was tested on the pilot-cohort of injected mice. Changes in heart rate, surface electrocardiogram, and respiratory responses were observed in response to both one- and two-photon photostimulation. The results demonstrate feasibility of retrograde labeling for organ targeted optical neuromodulation.
format	article
author	Arjun K. Fontaine Gregory L. Futia Pradeep S. Rajendran Samuel F. Littich Naoko Mizoguchi Kalyanam Shivkumar Jeffrey L. Ardell Diego Restrepo John H. Caldwell Emily A. Gibson Richard F. ff Weir
author_facet	Arjun K. Fontaine Gregory L. Futia Pradeep S. Rajendran Samuel F. Littich Naoko Mizoguchi Kalyanam Shivkumar Jeffrey L. Ardell Diego Restrepo John H. Caldwell Emily A. Gibson Richard F. ff Weir
author_sort	Arjun K. Fontaine
title	Optical vagus nerve modulation of heart and respiration via heart-injected retrograde AAV
title_short	Optical vagus nerve modulation of heart and respiration via heart-injected retrograde AAV
title_full	Optical vagus nerve modulation of heart and respiration via heart-injected retrograde AAV
title_fullStr	Optical vagus nerve modulation of heart and respiration via heart-injected retrograde AAV
title_full_unstemmed	Optical vagus nerve modulation of heart and respiration via heart-injected retrograde AAV
title_sort	optical vagus nerve modulation of heart and respiration via heart-injected retrograde aav
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/e5554b021ce340498706e2698c75bcce
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Optical vagus nerve modulation of heart and respiration via heart-injected retrograde AAV

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