Vagus nerve stimulation drives selective circuit modulation through cholinergic reinforcement

Bioelectronic medicine: Preclinical insights and clinical advances

https://doi.org/10.1016/j.brs.2023.02.003

Organ- and function-specific anatomical organization of vagal fibers supports fascicular vagus nerve stimulation

A fully implantable wireless bidirectional neuromodulation system for mice

Recent evidence has suggested that the carotid bodies might act as immunological sensors, detecting pro-inflammatory mediators and signalling to the central nervous system, which, in turn, orchestrates autonomic responses. Here, we demonstrated that the TNF-α receptor type I is expressed in the carotid bodies of rats. The systemic administration of TNF-α increased carotid body afferent discharge and activated glutamatergic neurons in the nucleus tractus solitarius (NTS) that project to the rostral ventrolateral medulla (RVLM), where the majority of pre-sympathetic neurons reside. The activation of these neurons was accompanied by generalized activation of the sympathetic nervous system. Carotid body ablation blunted the TNF-α-induced activation of RVLM-projecting NTS neurons and the increase in splanchnic sympathetic nerve activity. Finally, plasma and spleen levels of cytokines after TNF-α administration were higher in rats subjected to either carotid body ablation or splanchnic sympathetic denervation. Collectively, our findings indicate that the carotid body detects circulating TNF-α to activate a counteracting sympathetic anti-inflammatory mechanism.

https://biorxiv.org/content/10.1101/2021.10.20.463417v1.full.pdf

The Carotid Body Detects Circulating Tumor Necrosis Factor-Alpha to Activate a Sympathetic Anti-Inflammatory Reflex

Vagus nerve stimulation (VNS) suppresses inflammation and autoimmune diseases in preclinical and clinical studies The underlying molecular, neurological, and anatomical mechanisms have been well characterized using acute electrophysiological stimulation of the vagus However, there are several unanswered mechanistic questions about the effects of chronic VNS, which require solving numerous technical challenges for a long-term interface with the vagus in mice Here, we describe a scalable model for long-term VNS in mice developed and validated in four research laboratories We observed significant heart rate responses for at least 4 weeks in 60-90% of animals Device implantation did not impair vagus-mediated reflexes VNS using this implant significantly suppressed TNF levels in endotoxemia Histological examination of implanted nerves revealed fibrotic encapsulation without axonal pathology This model may be useful to study the physiology of the vagus and provides a tool to systematically investigate long-term VNS as therapy for chronic diseases modeled in mice

Development and characterization of a chronic implant mouse model for vagus nerve stimulation.

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Development and characterization of a chronic implant mouse model for vagus nerve stimulation.