Viral Labeling of the CNS Origins of the Sympathetic Nervous System Innervation of Brown Adipose Tissue: Implications for Torpor and Hibernation Responses

Abstract

Brown adipose tissue (BAT) is intimately involved in cold exposure- and overeating-induced thermogenesis. BAT receives a dense innervation by the sympathetic nervous system (SNS) and this innervation plays an important role in BAT thermogenic responses. The BAT pad receiving the most attention is interscapular BAT (IBAT) because of its size, accessibility and clear SNS innervation. Although the first neuroanatomical demonstration of IBAT sympathetic innervation was done using histofluorescence to visualize their catecholaminergic phenotype more than 35 years ago, the central nervous system (CNS) origins of this innervation were not identified neuroanatomically until recently in our laboratory. This was accomplished using a highly specific, transneuronal viral tract tracer — the Bartha’s K strain of the pseudorabies virus (PRV). PRV was injected into IBAT of Siberian hamsters and the infected neurons were visualized by immunocytochemistry. PRV-infected neurons were found in the spinal cord (intermediolateral cell group, central autonomic nucleus), brainstem (reticular area [lateral, intermediate, parvocellular, medullary and gigantocellular reticular nuclei], caudal raphe area [raphe pallidus and raphe obscurus nuclei], C1 adrenaline cells and rostroventrolateral medullary regions, nucleus of the solitary tract, lateral paragigantocellular nucleus and the raphe magnus), midbrain (central gray, dorsal raphe) and forebrain (suprachiasmatic nucleus [SCN], retrochiasmatic area, paraventricular hypothalamic nucleus [PVN], medial preoptic area, lateral hypothalamus, dorsal hypothalamic area, zona incerta, arcuate nucleus, lateral septal region, bed nucleus of the stria terminalis — almost no infected neurons were seen in the ventromedial hypothalamic nucleus). Possible roles of three of these virally labeled origins of SNS outflow from brain to BAT (SCN,PVN and raphe pallidus) were discussed in terms of possible roles in thermogenesis in general, and in torpor/hibernation, specifically.