Structure and Functions of the Vagus Nerve in Mammals Author: Matteo M Ottaviani1, Vaughan G Macefield2,3,4 Affiliation: <sup>1</sup> Department of Neurosurgery, Università Politecnica delle Marche, Ancona, Italy. <sup>2</sup> Baker Heart and Diabetes Institute, Melbourne, Australia. <sup>3</sup> Baker Department of Cardiometabolic Health, University of Melbourne, Melbourne, Australia. <sup>4</sup> Department of Anatomy &amp; Physiology, University of Melbourne, Melbourne, Australia. Conference/Journal: Compr Physiol Date published: 2022 Aug 11 Other: Volume ID: 12 , Issue ID: 4 , Pages: 1-49 , Special Notes: doi: 10.1002/cphy.c210042. , Word Count: 187 We review the structure and function of the vagus nerve, drawing on information obtained in humans and experimental animals. The vagus nerve is the largest and longest cranial nerve, supplying structures in the neck, thorax, and abdomen. It is also the only cranial nerve in which the vast majority of its innervation territory resides outside the head. While belonging to the parasympathetic division of the autonomic nervous system, the nerve is primarily sensory-it is dominated by sensory axons. We discuss the macroscopic and microscopic features of the nerve, including a detailed description of its extensive territory. Histochemical and genetic profiles of afferent and efferent axons are also detailed, as are the central nuclei involved in the processing of sensory information conveyed by the vagus nerve and the generation of motor (including parasympathetic) outflow via the vagus nerve. We provide a comprehensive review of the physiological roles of vagal sensory and motor neurons in control of the cardiovascular, respiratory, and gastrointestinal systems, and finish with a discussion on the interactions between the vagus nerve and the immune system. © 2022 American Physiological Society. Compr Physiol 12: 1-49, 2022. PMID: 35950655 DOI: 10.1002/cphy.c210042