Mapping the Central Autonomic Network Nodes Integrating Cardiovascular and Metabolic Control

The autonomic networks of the central nervous system tightly coordinate metabolic and cardiovascular functions. The frequent coexistence of metabolic and cardiovascular disorders suggests cross talk between neural circuits governing energy balance and cardiovascular regulation. In this study, we used trans-neuronal tracing to define the higher-order neurons involved in the coordination of cardiometabolic regulation in mice. We identified several nuclei that contain neurons associated with a cardiovascular organ (kidney) and metabolic tissues (brown adipose tissue [BAT] or liver), with substantial overlap across regions. Co-projecting neurons (kidney-BAT or kidney-liver) were observed in areas including the cortical, hypothalamic, midbrain, and brainstem regions. Analysis of soma size revealed regional and organ-specific differences, with some nuclei exhibiting multiple morphological phenotypes. Notably, soma size distributions differed significantly between kidney- and BAT-projecting neurons in the motor cortex and locus coeruleus, but not in the paraventricular nucleus or lateral hypothalamus. These findings indicate that while cardiometabolic control involves overlapping neuronal populations, morphological specialization may distinguish neurons regulating cardiovascular versus metabolic functions. Together, this work provides anatomical evidence supporting the integrative organization of autonomic networks that coordinate cardiovascular and metabolic regulation.