LAUSR

A defining characteristic of endotherms, including mammals, is a warm, highly regulated, and stable core body temperature (Tb). Identifying the network of neurons controlling Tb is essential for understanding this fundamental physiology. The preoptic area (POA) is a brain region that receives afferent and local Tb sensory information and harbors efferent neurons of autonomic and behavioral thermoregulatory pathways [1]. These pathways contribute to thermoregulatory behavior, shivering and non-shivering thermogenesis, cutaneous vasomotion and cardiovascular responses. Researchers have identified POA neuronal populations in mice that reduce Tb when activated, regulating heat defense, torpor, and thermoregulation during sleep. A dozen such populations are marked by the expression of genes encoding enzymes, neuropeptides, and/or receptors and are predominantly glutamatergic. Future studies will need to better characterize these heterogenous neuronal populations, uncovering overlaps and defining subpopulations with more precise roles. A POA population that increases Tb when activated has been proposed and likely uses glutamatergic projections to the dorsomedial hypothalamus (DMH) [2]. We have now identified POA neurons expressing bombesin-like receptor-3 (POA) as the first defined, specific population whose activation increases Tb [3]. This is driven by nonshivering thermogenesis through brown adipose tissue (BAT) activation, with concomitant increases in heart rate and blood pressure. BRS3 is an orphan G protein-coupled receptor in mammals, although both gastrin-releasing peptide and neuromedin B are endogenous ligands in some other vertebrates. Brs3 is expressed in limited hypothalamic and other brain regions and in some peripheral cells. Mice with germline ablation of Brs3 become obese and have a lower light phase resting Tb and resting heart rate. Ablation of Brs3 in glutamatergic neurons caused a similar obesity and Tb phenotype as the global Brs3 null mice, and reexpression of Brs3 only in glutamatergic neurons reversed the null phenotype. Thus, BRS3 function, during and/or after glutamatergic neuronal development, has a role in regulating Tb and other aspects of energy homeostasis. More recently, we used expression of BRS3 as a marker for identification of and genetic access to specific neuronal populations. Ablation or silencing of DMH or POA neurons did not produce obesity or affect mean light phase Tb [3,4], indicating that BRS3 functions may be redundant or dispersed among multiple neuronal populations. While POA neurons may not affect mean light phase Tb, we did find impairments (described below) in adaptions to changing ambient temperatures and larger Tb swings in mice with this population silenced.