RT Journal Article SR Electronic T1 Functional Vagotopy in the Cervical Vagus Nerve of the Domestic Pig: Implications for Vagus Nerve Stimulation JF bioRxiv FD Cold Spring Harbor Laboratory SP 856989 DO 10.1101/856989 A1 Megan L. Settell A1 Bruce E. Knudsen A1 Aaron M. Dingle A1 Andrea L. McConico A1 Evan N. Nicolai A1 James K. Trevathan A1 Erika K. Ross A1 Nicole A. Pelot A1 Warren M. Grill A1 Kenneth J. Gustafson A1 Andrew J. Shoffstall A1 Justin C. Williams A1 Weifeng Zeng A1 Samuel O. Poore A1 Luis C. Populin A1 Aaron J. Suminski A1 Kip A. Ludwig YR 2019 UL http://biorxiv.org/content/early/2019/12/02/856989.abstract AB Given current clinical interest in vagus nerve stimulation, there are surprisingly few studies characterizing the anatomy of the vagus nerve in large animal models as it pertains to on-and off-target engagement of local fibers. We sought to address this gap by evaluating vagal anatomy in the domestic pig, whose vagus nerve organization and size approximates the clinical environment. We provide data on key features across the cervical vagus nerve including diameter, number and diameter of fascicles, and distance of fascicles from the epineural surface where stimulating electrodes are placed. We also characterize the relative locations of the superior and recurrent laryngeal branches of the vagus that have been implicated in therapy limiting side effects with common electrode placement. We identify key variants across the cohort that may be important for vagus nerve stimulation with respect to changing sympathetic/parasympathetic tone, such as cross-connections to the sympathetic trunk. We discovered that cell bodies of pseudo-unipolar cells aggregate together to form a very distinct grouping within the nodose ganglia. This distinct grouping gives rise to a larger number of smaller fascicles as one moves caudally down the cervical vagus nerve. This often leads to a distinct bimodal organization, or ‘vagotopy’ that may be advantageous to exploit in design of electrodes/stimulation paradigms. Finally, we place our data in context of historic and recent histology spanning mouse, rat, canine, pig, non-human primate and human models, thus providing a comprehensive resource to understand similarities and differences across species.