Crosstalk in the Central Autonomic Neurocircuitry Underlying Cardiovascular and Metabolic Control

Abstract

Obesity associated cardiovascular risks such as hypertension are serious medical conditions that increase mortality. The brain autonomic networks play an important role in the regulation of cardiovascular function and metabolism. Therefore, obesity may represent a cardiovascular‐metabolic coupling and possible crosstalk in the central autonomic networks. We and others have previously shown the existence of shared nuclei in the autonomic networks innervating cardiovascular organs such as the kidney and metabolic organs such as the liver and brown adipose tissue (BAT). However, whether there are shared neurons within these nuclei associated with these three organs is unknown. To address this, two groups of mice received injections of pseudorabies virus (PRV) expressing a green fluorescent protein (GFP) into both kidneys and PRV expressing a red fluorescent protein (RFP) in either the interscapular BAT (iBAT) or the left lobe of the liver. The animals were sacrificed 5‐7 days post‐injection and perfused. The brains were extracted, sectioned at 50 µm thickness, stained, and imaged with confocal microscopy. Sections were matched to the mouse atlas (Franklin & Paxinos) and neurons co‐expressing GFP and RFP throughout the brain were identified. We found several nuclei in which neurons were co‐labeled with GFP (kidney) and RFP (BAT or liver). Interestingly, co‐expression does not appear limited to nuclei of specific regions in the brain. Instead, co‐expression was observed in many nuclei from cortical and subcortical regions to hypothalamic areas, midbrain, and brainstem nuclei. Indeed, co‐expressing neurons were observed in areas such as the cortical regions (motor cortex and amygdala), hypothalamic nuclei (paraventricular nucleus (PVN), lateral hypothalamus (LH), and dorsomedial hypothalamus (DMH)), midbrain regions such as the periaqueductal gray, and brainstem nuclei such as the locus coeruleus (LC). In general, there appeared to be two scenarios for shared nuclei: 1) in regions such as LH, nucleus of the solitary tract, and dorsal motor nucleus of vagus there was very little co‐expression, and 2) in regions such as PVN, DMH, LC, and motor cortex there was moderate to high levels of co‐expression. This is the first study to provide anatomical evidence for crosstalk between the autonomic networks regulating cardiovascular and metabolic functions. Moreover, our data demonstrate that crosstalk between the autonomic networks controlling cardiovascular and metabolic functions is distributed throughout the central nervous system.