An excitatory projection from median preoptic area to the dorsomedial hypothalamus contributes to the activation BAT thermogenesis (1104.28)

Disinhibition of brown adipose tissue (BAT) sympathoexcitatory neurons in the dorsomedial hypothalamus (DMH), by reduced discharge of their input from GABAergic, in the preoptic area (POA), is thought to be a key step in the cold-defense and febrile activations of BAT sympathetic nerve activity (SNA) and BAT thermogenesis. Here we present evidence supporting the hypothesis that a population of median preoptic area (MnPO) neurons projecting to the DMH provides the excitatory drive to DMH neurons that is essential for cold-defense and febrile BAT thermogenesis. To determine if the MnPO contains putative BAT thermogenesis-promoting neurons that are activated during cold exposure and project to DMH, we injected the retrograde tracer, CTb into DMH and exposed the rats to a cold (10°C) ambient temperature to elicit BAT thermogenesis. We observed a larger number of c-fos and CTb immunoreactive neurons in the MnPO of cold-exposed rats than in those maintained at 25°C, confirming the existence of cold-activated neurons in MnPO that project to DMH. In urethane/chloralose-anesthetized, Wistar rats, bilateral nanoinjection of the GABAA agonist, muscimol (120nl, 1mM), into the medial preoptic area (MPA), a region containing warm-sensitive neurons, did not decrease cold-evoked BAT SNA, consistent with the hypothesis that the MPA is not the source of DMH excitation required for BAT thermogenesis. However, subsequent nanoinjection of muscimol (120nl, 1mM) into the MnPO completely reversed cold-evoked BAT SNA. Moreover, in other experiments, the activation of BAT SNA following PGE2 nanoinjection into MPA was also inhibited by muscimol nanoinjection into MnPO. These data demonstrate that the MnPO contains essential thermogenesis-promoting, BAT sympathoexcitatory neurons.