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    Abstract:
    The vagus nerve plays an important role in the regulation of organ function, including reflex pathways that regulate immunity and inflammation. Recent studies using genetically modified mice have improved our understanding of molecular mechanisms in the neural control of immunity. However, mapping neural signals transmitted in the vagus nerve in mice has been limited by technical challenges. Here, we have standardized an experimental protocol to record compound action potentials transmitted in the vagus nerve.The vagus nerve was isolated in Balb/c and B6.129S mice, and placed either on a hook or cuff electrode. The electrical signals from the vagus nerve were digitized using either a Neuralynx or Plexon data acquisition system. Changes in the vagus nerve activity in response to anesthesia, feeding and administration of bacterial endotoxin were analyzed.We have developed an electrophysiological recording system to record compound action potentials from the cervical vagus nerve in mice. Cuff electrodes significantly reduce background noise and increase the signal to noise ratio as compared to hook electrodes. Baseline vagus nerve activity varies in response to anesthesia depth and food intake. Analysis of vagus neurograms in different mouse strains (Balb/c and C57BL/6) reveal no significant differences in baseline activity. Importantly, vagus neurogramactivity in wild type and TLR4 receptor knock out mice exhibits receptor dependency of endotoxin mediated signals.These methods for recording vagus neurogram in mice provide a useful tool to further delineate the role of vagus neural pathways in a standardized murine disease model.
    Keywords:
    Vagus Nerve Stimulation
    The diverse array of end organ innervations of the vagus nerve, coupled with increased basic science evidence, has led to vagus nerve stimulation becoming a management option in a number of clinical disorders. This review discusses methods of electrically stimulating the vagus nerve and its current and potential clinical uses.
    Vagus Nerve Stimulation
    Clinical Practice
    Oculocardiac 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.
    Vagus Nerve Stimulation
    Citations (36)
    In a previous paper, the anatomy and physiology of the vagus nerve was discussed in an attempt to explain which vagus nerve fibers and branches are affected by clinically relevant electrical stimulation. This companion paper presents some of vagus nerve stimulation's putative central nervous system mechanisms of action by summarizing known anatomical projections of vagal afferents and their effects on brain biogenic amine pathways and seizure expression.
    Vagus Nerve Stimulation
    Oculocardiac reflex
    Citations (167)
    Abstract The vagus nerve, the great wanderer, is involved in numerous processes throughout the body and vagus nerve stimulation (VNS) has the potential to modulate many of these functions. This wide-reaching capability has generated much interest across a range of disciplines resulting in several clinical trials and studies into the mechanistic basis of VNS. This review discusses current preclinical and clinical evidence supporting the efficacy of VNS in different diseases and highlights recent advancements. Studies that provide insights into the mechanism of VNS are considered.
    Vagus Nerve Stimulation
    Citations (46)
    The authors studied human vagus nerve electrophysiology intraoperatively on 21 patients (age range: 4 to 31 years) during implantation of a vagus nerve stimulator for seizure control. The study was performed with direct electrical stimulation of the vagus nerve with various stimulation parameters resembling those employed by the Cyberonics NeuroCybernetic Prosthesis System (Houston, TX), which is used clinically for vagus nerve stimulation for treatment of seizures. Recordings were made directly from the rostral end of the vagus nerve. The response of the vagus nerve to various stimulus parameters in patients of different ages was studied. Based on the vagus nerve characteristics, age-related adjustments for stimulus parameters were recommended.
    Vagus Nerve Stimulation
    Oculocardiac reflex
    Stimulus (psychology)