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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Fractal Microelectrodes for More Energy‐Efficient Cervical Vagus Nerve Stimulation
Vagus nerve stimulation (VNS) has the potential to treat various peripheral dysfunctions, but the traditional cuff electrodes for VNS are susceptible to off‐target effects. Microelectrodes may enable highly selective VNS that can mitigate off‐target effects, but they suffer from the increased impedance. Recent studies on microelectrodes with non‐Euclidean geometries have reported higher energy efficiency in neural stimulation applications. These previous studies use electrodes with mm/cm‐scale dimensions, mostly targeted for myelinated fibers. This study evaluates fractal microelectrodes for VNS in a rodent model (
- NSF-PAR ID:
- 10408562
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Advanced Healthcare Materials
- Volume:
- 12
- Issue:
- 19
- ISSN:
- 2192-2640
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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After sensory information is encoded into neural signals at the periphery, it is processed through multiple brain regions before perception occurs (i.e., sensory processing). Recent work has begun to tease apart how neuromodulatory systems influence sensory processing. Vagus nerve stimulation (VNS) is well-known as an effective and safe method of activating neuromodulatory systems. There is a growing body of studies confirming VNS has immediate effects on sensory processing across multiple sensory modalities. These immediate effects of VNS on sensory processing are distinct from the more well-documented method of inducing lasting neuroplastic changes to the sensory pathways through repeatedly delivering a brief VNS burst paired with a sensory stimulus. Immediate effects occur upon VNS onset, often disappear upon VNS offset, and the modulation is present for all sensory stimuli. Conversely, the neuroplastic effect of pairing sub-second bursts of VNS with a sensory stimulus alters sensory processing only after multiple pairing sessions, this alteration remains after cessation of pairing sessions, and the alteration selectively affects the response properties of neurons encoding the specific paired sensory stimulus. Here, we call attention to the immediate effects VNS has on sensory processing. This review discusses existing studies on this topic, provides an overview of the underlying neuromodulatory systems that likely play a role, and briefly explores the potential translational applications of using VNS to rapidly regulate sensory processing.more » « less
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Abstract Objective . Vagus nerve stimulation (VNS) has been FDA-approved as a long-term, therapeutic treatment for multiple disorders, including pharmacoresistant epilepsy and depression. Here we elucidate the short-term effects of VNS on sensory processing.Approach . We employed an information theoretic approach to examine the effects of VNS on thalamocortical transmission of sensory-related information along the somatosensory pathway.Main results . We found that VNS enhanced the selectivity of the response of thalamic neurons to specific kinetic features in the stimuli, resulting in a significant increase in the efficiency and rate of stimulus-related information conveyed by thalamic spikes. VNS-induced improvements in thalamic sensory processing coincided with a decrease in thalamic burst firing. Importantly, we found VNS-induced enhancement of sensory processing had a rapid onset and offset, completely disappearing one minute after cessation of VNS. The timescales of these effects indicate against an underlying mechanism involving long-term neuroplasticity. We found several patterns of VNS (tonic, standard duty-cycle, and fast duty-cycle) all induced similar improvements in sensory processing. Under closer inspection we noticed that due to the fast timescale of VNS effects on sensory processing, standard duty-cycle VNS induced a fluctuating sensory processing state which may be sub-optimal for perceptual behavior. Fast duty-cycle VNS and continuous, tonic VNS induced quantitatively similar improvements in thalamic information transmission as standard duty-cycle VNS without inducing a fluctuating thalamic state. Further, we found the strength of VNS-induced improvements in sensory processing increased monotonically with amplitude and frequency of VNS.Significance . These results demonstrate, for the first time, the feasibility of utilizing specific patterns of VNS to rapidly improve sensory processing and confirm fast duty-cycle and tonic patterns as optimal for this purpose, while showing standard duty-cycle VNS causes non-optimal fluctuations in thalamic state. -
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Abstract To treat diseases associated with vagal nerve control of peripheral organs, it is necessary to selectively activate efferent and afferent fibers in the vagus. As a result of the nerve’s complex anatomy, fiber-specific activation proves challenging. Spatially selective neuromodulation using micromagnetic stimulation(
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