In vivo holographic photo-stimulation and two photon GCaMP6 imaging of vagus nerve axons using a GRIN lens integrated nerve cuff

Futia, Gregory L.; Fontaine, Arjun K.; Littich, Samuel F.; McCullough, Connor; Restrepo, Diego; Weir, Richard F.; Caldwell, John H.; Gibson, Emily A.

doi:10.1117/12.2521830

Cited by 2 publications

(4 citation statements)

References 17 publications

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“…A custom setup for two-photon imaging and holographic photostimulation was built on a Movable Objective Microscope (Sutter Instruments, Inc.), as described previously 34 and shown schematically in Supplementary Fig. 2.…”

Section: Grin Lens-integrated Cervical Nerve Cuffmentioning

confidence: 99%

“…We demonstrate feasibility of this approach with injection of a retrograde AAV (rAAV2-retro) into the ventricular myocardium to transduce opsins proximally in fibers of the vagus nerve. Photostimulation of subsets of heart-specific axons was applied at the cervical vagus nerve using both one-photon illumination and two-photon holographic excitation 33,34 . Significant changes in heart rate and electrocardiogram (ECG) parameters, as well as the elicitation of respiratory reflex, serve as a proof-of-concept for organ-specific optogenetic neuromodulation and study of organ function.…”

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confidence: 99%

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

Fontaine

Futia

Rajendran

et al. 2021

Sci Rep

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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.

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Section: Grin Lens-integrated Cervical Nerve Cuffmentioning

confidence: 99%

mentioning

confidence: 99%

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

Fontaine

Futia

Rajendran

et al. 2021

Sci Rep

Self Cite

View full text Add to dashboard Cite

show abstract

“…We demonstrate this approach with injection of a retrograde AAV into the heart to transduce opsins proximally in fibers of the vagus nerve. Selective photostimulation of subsets of heart-specific axons was applied at the cervical vagus nerve using both one-photon illumination and two-photon holographic excitation 33,34 .…”

Section: Vagus Nerve Stimulation (Vns) Interventions Using Electrode-mentioning

confidence: 99%

“…Objective Microscope (Sutter Instruments, Inc.), as described previously 34 and shown schematically in Supplementary Figure1. A Ti:Sapphire laser oscillator (MaiTai HP, Newport, Inc.) producing ~80 fs pulses at 920 nm with an 80 MHz repetition rate provided the excitation light for two-photon imaging.…”

Section: A Custom Setup For Imaging and Holographic Photostimulation mentioning

confidence: 99%

Selective Modulation of Heart and Respiration by Optical Control of Vagus Nerve Axons Innervating the Heart

Fontaine

Futia

Rajendran

et al. 2020

Preprint

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AbstractTargeting specifics subsets of peripheral pathways of the autonomic nervous system will enable new avenues to study organ control and develop new disease therapies. Vagus nerve stimulation (VNS) has shown many therapeutic benefits but current approaches involve imprecise electrical stimulation that gives rise to adverse effects, and the functionally relevant pathways are poorly understood. One method to overcome these limitations is the use of optogenetic techniques, which facilitate highly specific neural communication with light-sensitive actuators (opsins). Opsins can be targeted to cell populations of interest based on the location of viral delivery and genetic control of expression. Here, we tested whether holographic photostimulation of subsets of axons of the cervical vagus nerve that innervate the heart can be used to modulate cardiac function. Viral injection of retrograde adeno-associated virus (rAAV2-retro) in the heart resulted in robust, primarily afferent, opsin reporter expression in the vagus nerve, nodose ganglion, and brainstem. Selective holographic photostimulation of axons resulted in changes in heart rate, surface cardiac electrogram, and respiratory responses that were different from responses elicited by whole nerve photostimulation.

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In vivo holographic photo-stimulation and two photon GCaMP6 imaging of vagus nerve axons using a GRIN lens integrated nerve cuff

Cited by 2 publications

References 17 publications

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

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

Selective Modulation of Heart and Respiration by Optical Control of Vagus Nerve Axons Innervating the Heart

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