Physiology and Pharmacology of BRS3 (Bombesin Receptor Subtype-3)

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Progress in FY2023 includes the following: We have identified preoptic area neurons expressing BRS3 (POA-BRS3) as a population whose activation increased body temperature; inversely, acute inhibition of these neurons reduced body temperature. POA-BRS3 neurons that project to either the paraventricular nucleus of the hypothalamus or the dorsomedial hypothalamus increased body temperature, heart rate, and blood pressure via the sympathetic nervous system. Long-term inactivation of POA-BRS3 neurons caused increased body temperature variability, overshooting both increases and decreases in body temperature set point, with RNA expression profiles suggesting multiple types of POA-BRS3 neurons. Thus, POA-BRS3 neuronal populations regulate body temperature and heart rate, contribute to cold defense, and fine-tune feedback control of body temperature. These findings advance understanding of homeothermy, a defining feature of mammalian biology. We are now generating Brs3-FlpO and Brs3-Dre recombinase driver mouse lines. These enable combinatorial approaches to identifying and determining the functions of smaller populations of neurons that are better defined.