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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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Multi-Channel Microscale Nerve Cuffs for Spatially Selective Neuromodulation
Peripheral nerve modulation via electrical stimulation shows promise for treating several diseases, but current approaches lack selectivity, leading to side effects. Exploring selective neuromodulation with commercially available nerve cuffs is impractical due to their high cost and limited spatial resolution. While custom cuffs reported in the literature achieve high spatial resolutions, they require specialized microfabrication equipment and significant effort to produce even a single design. This inability to rapidly and cost-effectively prototype novel cuff designs impedes research into selective neuromodulation therapies in acute studies. To address this, we developed a reproducible method to easily create multi-channel epineural nerve cuffs for selective fascicular neuromodulation. Leveraging commercial flexible printed circuit (FPC) technology, we created cuffs with high spatial resolution (50 μm) and customizable parameters like electrode size, channel count, and cuff diameter. We designed cuffs to accommodate adult mouse or rat sciatic nerves (300–1500 μm diameter). We coated the electrodes with PEDOT:PSS to improve the charge injection capacity. We demonstrated selective neuromodulation in both rats and mice, achieving preferential activation of the tibialis anterior (TA) and lateral gastrocnemius (LG) muscles. Selectivity was confirmed through micro-computed tomography (μCT) and quantified through a selectivity index. These results demonstrate the potential of this fabrication method for enabling selective neuromodulation studies while significantly reducing production time and costs compared to traditional approaches.
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- PAR ID:
- 10541909
- Publisher / Repository:
- MDPI Micromachines
- Date Published:
- Journal Name:
- Micromachines
- Volume:
- 15
- Issue:
- 8
- ISSN:
- 2072-666X
- Page Range / eLocation ID:
- 1036
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.3390/mi15081036
