Polysynaptic Neurotracing of Autonomic Nuclei Involved in Liver and Kidney Function

Abstract

Central nervous system (CNS) autonomic network plays an important role in the control of hepatic and renal functions with important implications in obesity and related hypertension. Previous studies employing pseudorabies viruses (PRV) have provided insight into the polysynaptic connections between various CNS nuclei and liver or kidney. However, whether the same autonomic network is involved in the control of hepatic and renal function remain unknown. Therefore, we used two groups of animals that received injections of PRV that express a green fluorescent protein (PRV‐GFP) into the left lobe of the liver or the two kidneys to compare labeled nuclei. The animals were sacrificed 5, 6, or 7 days after PRV injections, perfused, and the brains extracted. The brains were sectioned at 50 μm thickness, stained for GFP, and imaged with confocal microscopy. Sections were matched to the mouse atlas (Franklin & Paxinos, 3rd ed, 2008) and nuclei identified. Consistent with published work, we identified several nuclei that project to both the liver and kidneys 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 both liver and kidneys infections while the dorsal vagal nucleus expressed GFP after inoculation of the liver, but less after the kidneys. A few nuclei were observed in the midbrain after liver and kidneys infections, yet the ventral tegmental area projections observed previously from the liver were also observed from the kidneys which has not been previously reported. GFP staining was noted in several hypothalamic nuclei such as the paraventricular nucleus, arcuate nucleus, lateral hypothalamus, and dorsomedial hypothalamus after PRV infections of both organs. Projections from the cortical region and other areas such as the motor cortex, bed nucleus of the striatum, septal nuclei, and preoptic nuclei were also observed. In addition, we identified several nuclei such as the subfornical organ, nucleus accumbens, and insular cortex that project to the liver or kidneys which have not been previously reported and a few nuclei that were specific to the liver or kidneys. Our study supports the existence of an overlap in the projections that sub‐serve the liver and kidneys. The relevance of the newly identified autonomic projections to hepatic and renal functions is under investigation.