Anatomical Distribution of Cardiac Vagal Motor Neurons in Dorsal Motor Nucleus of the Vagus

Cardiac vagal motor neurons (CVNs) send direct axonal innervations through the vagus nerve to innervate cardiac ganglia critical in the regulation of chronotropy. Historically, CVNs in the brainstem’s nucleus ambiguus (CVN NA ) were the focus of research on central circuit examinations for cardiac vagal control. However, motor neurons in the brainstem’s dorsal motor nucleus of the vagus (DMV), known for innervating organs critical in gastrointestinal function, can also be retrogradely traced from cardiac tissue and upon activation cause cardio inhibition. To further explore CVNs in DMV (CVN DMV ), this study hypothesized that the anatomical distribution of CVN DMV found by using retrograde tracing from cardiac tissue in adult mice would be similar to the columnar organization of gastrointestinal projecting neurons. C57/Bl6J mice 7-11 weeks of age were cardiac injected with the retrograde tracer Fluorogold (40ul [1-2%]) followed by transcardial perfusion 2-3 weeks later. CVN DMV were found along the entire rostro caudal extent of DMV. However, there was a significantly larger population of CVN DMV in more caudal locations near the caudal aspect of area postrema (AP; 11±1 CVN DMV at -7.60mm vs 4±1 at –6.9mm; p=0.0271). The locations of CVN DMV also have significant overlap with the rostro-caudal distribution of CVN NA although CVN DMV (as with all of DMV compared with NA) were more prevalent in the caudal extent of the brainstem (-7.86mm from bregma; 7±2 CVN DMV vs 2±1 CVN NA ; p=0.0238). Total CVN DMV count distribution was bilaterally symmetrical with no significant differences between hemispheres (16±2 CVN DMV in left vs 18±3 in right, p=0.1856). To determine if CVN DMV existed in a columnar distribution, the mediolateral distribution of CVN DMV was examined by dividing DMV in each hemisphere into thirds. When divided by hemisphere, CVN DMV occupying the right hemisphere were significantly lateralized from midline with cell counts significantly greater in the lateral third of DMV (10±1 CVN DMV ) compared to the medial third (3±1 CVN DMV ; p=0.0017). This lateralization in the right hemisphere was most pronounced at rostro caudal locations again near caudal AP (-7.86mm to -7.60mm from bregma; medial vs lateral, p=<0.001). A similar lateralization was not present in the left hemisphere (5±1 CVN DMV in lateral third vs 5±0 in medial third; p=0.9969). Since other organ projections demonstrate robust columnar organization, dual retrograde injections were conducted to examine potential co-labeling between CVN DMV and gastric projecting DMV (GVN) due to GVNs high abundance in DMV. Specifically examining rostro caudal positions -7.86mm and –7.60mm from bregma. Despite robust labeling for both CVN and GVN, only ~2.5% of total neurons (CVN + GVN) were found to be co-labeled. More specifically this broke down to ~7.5% of total CVN, and ~4.5% of total GVN that were found to be co-labeled. Taken together, these data indicate that CVN DMV conforms to the columnar organization of DMV, but contrasts to most other organ projections due to prominent lateralization present in the right hemisphere. Furthermore, co-labeling of CVN DMV with GVN does exist, albeit in limited numbers, raising questions about how many neurons are required to coordinate any given homeostatic function and whether DMV serves as a major integrative site for parasympathetic homeostatic function. Future directions will also include dual retrograde injections of cardiac and hepatic tissue, since unlike GVN, hepatic projecting neurons in DMV are also highly lateralized. R01HL157366 NIHLB to CRB This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.