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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.
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Details
1 University of Colorado - Anschutz Medical Campus, Departments of Bioengineering, Aurora, USA (GRID:grid.430503.1) (ISNI:0000 0001 0703 675X); University of Colorado - Anschutz Medical Campus, Biomechatronics Development Laboratory, Aurora, USA (GRID:grid.430503.1) (ISNI:0000 0001 0703 675X)
2 University of Colorado - Anschutz Medical Campus, Departments of Bioengineering, Aurora, USA (GRID:grid.430503.1) (ISNI:0000 0001 0703 675X)
3 University of California Los Angeles, UCLA Cardiac Arrhythmia Center, Los Angeles, USA (GRID:grid.19006.3e) (ISNI:0000 0000 9632 6718); University of California Los Angeles, UCLA Neurocardiology Research Program of Excellence, Los Angeles, USA (GRID:grid.19006.3e) (ISNI:0000 0000 9632 6718)
4 University of Colorado - Anschutz Medical Campus, Departments of Cell and Developmental Biology, Aurora, USA (GRID:grid.430503.1) (ISNI:0000 0001 0703 675X); Meikai University School of Dentistry, Division of Pharmacology, Department of Diagnostic and Therapeutic Sciences, Saitama, Japan (GRID:grid.411767.2) (ISNI:0000 0000 8710 4494)
5 University of Colorado - Anschutz Medical Campus, Departments of Cell and Developmental Biology, Aurora, USA (GRID:grid.430503.1) (ISNI:0000 0001 0703 675X)
6 University of Colorado - Anschutz Medical Campus, Departments of Bioengineering, Aurora, USA (GRID:grid.430503.1) (ISNI:0000 0001 0703 675X); University of Colorado - Anschutz Medical Campus, Biomechatronics Development Laboratory, Aurora, USA (GRID:grid.430503.1) (ISNI:0000 0001 0703 675X); Rocky Mountain Veterans Affairs Medical Center (VAMC), Aurora, USA (GRID:grid.422100.5) (ISNI:0000 0000 9751 469X)