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

二零二三财年的进展包括以下各项： 我们已经确定视前区神经元表达BRS 3（POA-BRS 3）作为一个人口的激活增加体温，相反，急性抑制这些神经元降低体温。投射到下丘脑室旁核或背内侧下丘脑的POA-BRS 3神经元通过交感神经系统增加体温、心率和血压。POA-BRS 3神经元的长期失活导致体温变异性增加，超过体温设定点的增加和降低，RNA表达谱表明多种类型的POA-BRS 3神经元。因此，POA-BRS 3神经元群体调节体温和心率，有助于寒冷防御，并微调体温的反馈控制。这些发现促进了对恒温的理解，恒温是哺乳动物生物学的一个定义性特征。 我们现在正在产生Brs 3-FlpO和Brs 3-Dre重组酶驱动小鼠系。这些使组合方法能够识别和确定更好定义的较小神经元群体的功能。

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.