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Cytokine-specific Neurograms in the Sensory Vagus Nerve
Open accessAbstract
The axons of the sensory, or afferent, vagus nerve transmit action potentials to the central nervous system in response to changes in the body's metabolic and physiological status. Recent advances in identifying neural circuits that regulate immune responses to infection, inflammation and injury have revealed that vagus nerve signals regulate the release of cytokines and other factors produced by macrophages. Here we record compound action potentials in the cervical vagus nerve of adult mice and reveal the specific activity that occurs following administration of the proinflammatory cytokines tumor necrosis factor (TNF) and interleukin 1β (IL-1β). Importantly, the afferent vagus neurograms generated by TNF exposure are abolished in double knockout mice lacking TNF receptors 1 and 2 (TNF-R1/2KO), whereas IL-1β-specific neurograms are eliminated in knockout mice lacking IL-1β receptor (IL-1RKO). Conversely, TNF neurograms are preserved in IL-1RKO mice, and IL-1β neurograms are unchanged in TNF-R1/2KO mice. Analysis of the temporal dynamics and power spectral characteristics of afferent vagus neurograms for TNF and IL-1β reveals cytokine-selective signals. The nodose ganglion contains the cell bodies of the sensory neurons whose axons run through the vagus nerve. The nodose neurons express receptors for TNF and IL-1β, and we show that exposing them to TNF and IL-1β significantly stimulates their calcium uptake. Together these results indicate that afferent vagus signals in response to cytokines provide a basic model of nervous system sensing of immune responses.
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“Using bipolar electrodes, Steinberg et al. [13] recently demonstrated cytokine-specific neurograms in the sensory vagus nerve in mice.”
From A novel flexible cuff-like microelectrode for dual purpose, acute and chronic electrical interfacing with the mouse cervical vagus nerve (2017) · cites this paper as [13]
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- Huerta PT, Olofsson PS. (2016) Bioelectronic medicine: Harnessing the electric patterns of neurons for therapy. Technical workshop W06 at the 10th Forum of Neuroscience, Copenhagen, Denmark. FENS; c.2016 [updated 2016 Jun 30; cited 2016 Dec 8]. Available from: https://doi.org/forum2016.fens.org/forum-programme/preliminary-programme/
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Metadata
- Authors
- Steinberg, B. E., Silverman, H. A., Robbiati, S., Gunasekaran, M. K., Tsaava, T., Battinelli, E., Stiegler, A., Bouton, C. E., Chavan, S. S., Tracey, K. J., & Huerta, P. T.
- Affiliations
- Northwell Health (US)
- Circulatory Technology (United States) (US)
- Corresponding author
- Tracey, Kevin J.
- Huerta, Patricio T.
- ORCID
- Venue
- Bioelectronic Medicine
- Published
- 2016-06
- Volume
- 3
- Issue
- 1
- Pages
- 7-17
- ISSN
- 2332-8886 (ISSN-L)
- PMC
- PMC6039192
- OpenAlex
- W2898217533
- Cited by
- 168
- References
- 26
- Citations by year
- 2026: 22 · 2025: 17 · 2024: 15 · 2023: 24 · 2022: 24 · 2021: 15 · 2020: 17 · 2019: 20 · 2018: 8 · 2017: 5
- FWCI
- 6.03
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc-nd
- creativecommons.org/licenses/by/4.0 (tdm)
- Locations
- Bioelectronic Medicine (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institutes of Health
- Defense Advanced Research Projects Agency (W911NF-09-1-0125)
- Advanced Research Projects Agency
- National Institute of Allergy and Infectious Diseases (P01AI102852, P01AI073693)
- Topics
- Life Sciences › Neuroscience › Neurology › Vagus Nerve Stimulation Research
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Rate Variability and Autonomic Control
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Keywords
- vagus nerve, cytokine signaling, TNF-α, IL-1β, nodose ganglion, sensory neurons, calcium uptake, immune sensing, neuroimmune interactions, compound action potential
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