Defining the Neurocircuit Underlying Autonomic Control of Cardiovascular and Metabolic Functions

Paul Williams; Deng Guo; Kamal Rahmouni

doi:10.1096/fasebj.2021.35.S1.02863

The central nervous system (CNS) autonomic network play an important role in energy homeostasis, and cardiovascular regulation with important pathophysiological implications. However, whether the same autonomic network is involved in metabolic and cardiovascular control remain unknown. We hypothesize that divergent neurocircuits are involved in the energy balance and cardiovascular regulation. To test this, we employed pseudorabies viruses expressing a green fluorescent protein (PRV‐GFP) to understand the polysynaptic connections between CNS nuclei and metabolic organs (liver and brown adipose tissue [BAT]) vs a key cardiovascular organ (kidney). 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 (nTS) 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 BAT. 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, BAT, and kidneys, whereas a few nuclei such as the nucleus accumbens, and insular cortex project specifically to the liver. GFP expression was noted in several hypothalamic nuclei such as the paraventricular nucleus, arcuate nucleus, lateral hypothalamus, and ventromedial hypothalamus (VMH) for all three organs. To define the specific neuronal populations projecting to various organs, we used mice bearing Cre‐mediated expression of a fluorescent protein, td‐Tomato. We injected PRV‐GFP into the kidneys of animals expressing td‐Tomato in the steroidogenic factor‐1 (SF‐1) neurons located in the VMH. Substantial number of VMH SF‐1 neurons were labeled with GFP following PRV inoculation in the kidneys. Moreover, we identified several downstream nuclei that receive SF‐1 neuron projections where GFP is expressed including the nTS, periaqueductal grey, and amygdala. Our study supports the existence of an overlap, but also unique, projections that sub‐serve the liver, BAT, and kidneys. We also established that SF‐1 neurons are part of the renal autonomic network. The relevance of the newly identified autonomic projections to hepatic, BAT, and renal functions is under investigation.

Defining the Neurocircuit Underlying Autonomic Control of Cardiovascular and Metabolic Functions

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