Abstract

Central nervous system (CNS) autonomic network plays an important role in energy homeostasis, and cardiovascular function with important pathophysiological implications. Previous studies employing pseudorabies viruses (PRV) have provided insight into the polysynaptic connections between CNS nuclei and liver, adipose tissue, or kidney. However, whether the same autonomic network is involved in the control of these three organs remain unknown. Therefore, three groups of mice received injections of PRV expressing a green fluorescent protein (GFP) into the left lobe of the liver, interscapular brown adipose tissue (iBAT), or the kidneys to compare their neuronal projections. The animals were sacrificed 5, 6, or 7 days post-injection, perfused, the brains extracted, sectioned at 50 μm thickness, stained for GFP, and imaged with confocal microscopy. Sections were matched to the mouse atlas (Franklin & Paxinos) and nuclei identified. We identified several nuclei that project to all three organs although they may represent different orders (expression appearing on different days). In the brainstem, the nucleus of the solitary tract and area postrema expressed GFP after infection of the three organs while the dorsal vagal nucleus expressed GFP after infection of the liver, but less after inoculation of the kidneys. We found GFP expression in the ventral tegmental area following liver infection and after inoculation of the kidneys or iBAT. GFP expression was noted in several hypothalamic nuclei such as the paraventricular nucleus, arcuate nucleus, lateral hypothalamus, and dorsomedial hypothalamus for all three organs. Projections from cortical and subcortical regions such as the motor cortex, bed nucleus of the striatum, septal nuclei, and preoptic nuclei were also observed from the three organs. We observed that the subfornical organ project to the liver, iBAT, and kidneys, whereas a few nuclei such as the nucleus accumbens, and insular cortex project specifically to the liver. Our study supports the existence of an overlap, but also unique, projections that sub-serve the liver, iBAT, and kidneys. The relevance of the newly identified autonomic projections to hepatic, iBAT, and renal functions is under investigation.

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