Cholinergic neurons in the dorsal motor nucleus of the vagus contribute to vagally mediated cardiovascular responses through a putative pathway involving the nodose ganglion
The baroreflex plays an important role in maintaining cardiovascular homeostasis. Although the central pathways mediating baroreflex responses have been characterized, the mechanisms underlying modulation of vagal afferent signaling remain incompletely understood. We hypothesized that a neural circuit involving the dorsal motor nucleus of the vagus (DMV), a brainstem parasympathetic nucleus, contributes to vagally mediated cardiovascular responses. To examine the anatomical and functional relationship between the nodose ganglion of the vagus (NGV) and the DMV, we assessed cardiovascular responses to vagal afferent stimulation and performed neuronal tracing analyses. Vagal afferent stimulation increased c-Fos expression in the DMV. Denervation of cholinergic neurons in the DMV attenuated depressor and bradycardic responses to vagal stimulation. Anatomical evidence suggests reciprocal projections between the NGV and DMV, including glutamatergic inputs to the DMV and cholinergic fibers derived from the DMV within the NGV. Carbachol administration into the NGV induced depressor and bradycardic responses, which were abolished by atropine and attenuated by blockade of glutamatergic signaling in the DMV. These findings support the presence of a putative NGV–DMV pathway and indicate that cholinergic neurons in the DMV contribute to vagally mediated cardiovascular responses. This putative pathway may represent a previously unrecognized mechanism contributing to autonomic cardiovascular regulation.
Authors
- Takeshi Tokudome (ORCID: https://orcid.org/0000-0002-9117-3550)
- Yuka Nakao
- Daiki Masukawa (ORCID: https://orcid.org/0000-0002-3094-0058)
- Kazuto Kobayashi (ORCID: https://orcid.org/0000-0002-7617-2939)
- Kayo Nishizawa (ORCID: https://orcid.org/0009-0002-8398-588X)
- Natsuki Matsushita (ORCID: https://orcid.org/0000-0003-2618-7152)
- Toshihide Yamashita (ORCID: https://orcid.org/0000-0003-4559-7018)
- Yuki Fujita (ORCID: https://orcid.org/0009-0006-8347-3453)
- Haruhiko Bito
Institutions
- Fukushima Medical University (JP)
- Aichi Medical University (JP)
- Shimane University (JP)
- The University of Tokyo (JP)
- Yokohama City University (JP)
- The University of Osaka (JP)
Publication Details
- Journal
- Journal of Pharmacological Sciences
- Published
- 2026-08-27
- DOI
- https://doi.org/10.1016/j.jphs.2026.08.003
- Primary Topic
- Vagus Nerve Stimulation Research
- Type
- article
- Field-Weighted Citation Impact
- 0.00