Abstract P064: Anatomical Substrate For Leptin Control Of Central Autonomic Network Regulating Cardiovascular And Metabolic Functions

Leptin, a hormone secreted by adipose tissue, is a critical signal influencing energy balance and blood pressure through modulation of the autonomic nervous system. However, the anatomical substrates for leptin regulation of the central autonomic network underlying cardiovascular and metabolic functions remains unknown. Here, we used a retrograde pseudorabies virus encoding a green fluorescent protein (PRV-GFP) in mice expressing a red fluorescent (td-Tomato) in leptin receptor (LepR) neurons to map the LepR neurons that project polysynaptically to the kidneys, the left lobe of the liver, or the interscapular brown adipose tissue (iBAT). The animals were sacrificed at 5-, 6-, or 7-days post-PRV injection, the brain imaged using confocal microscopy, and co-localization quantified. We identified approximately 100 nuclei containing LepR neurons and more than 60 nuclei expressing GFP after PRV-GFP inoculation of the kidney, liver, or iBAT. Interestingly, 42 nuclei that express LepR neurons (tdTomato) also express GFP after PRV-GFP inoculation of either kidney, liver, or iBAT. Of these shared nuclei, we observed co-expression of tdTomato and GFP in only a few nuclei. After inoculation of PRV-GFP into kidneys, 25% of GFP expressing neurons in the preoptic (PO) nucleus co-localized with tdTomato while 3% co-localization was noted in the lateral hypothalamus (LH), and 1% in the nucleus of the solitary tract (nTS). For the liver, 35% co-localization was observed in the PO and 2.5% in the LH. For the iBAT, 20% co-localization was seen in the PO, 1.5% in the LH, and 8% in the nTS. Co-localization was also observed in other areas such as the septal nucleus, arcuate nucleus, dorsal and ventral medial hypothalamus, periaqueductal gray, and ventral tegmental area. In summary, LepR neurons projecting to the kidney, liver, or iBAT are present in specific regions such as the preoptic nuclei, some hypothalamic areas, and the nTS with the level of co-localization dependent on the organ. Our data suggest that although LepR neurons are distributed throughout the brain, those associated with the autonomic networks controlling cardiovascular and metabolic functions reside in specific regions of the brain.