ROLE OF GALANIN-EXPRESSING LEPTIN RECEPTOR NEURONS IN LEPTIN ACTION

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 中心，不一定是研究者的机构。 具体目标 我们推测，在扩展穹窿周围区（exPFA），特别是LepRb（Gal）神经元，LepRb神经元，通过PVN的输出介导的xigigenic瘦素的行动，从而控制摄食行为中发挥了至关重要的作用。我们的总体目标是了解LepRb（Gal）神经元的生理功能和潜在的神经元网络，以及研究exPFA中LepRb神经元的总体群体。因此，我们将： 1. 确定LepRb（Gal）神经元在生理性瘦素作用中的作用。我们将检查甘丙肽神经元中LepRb靶向缺失的小鼠（LepRbKO（Gal）小鼠）的表型，以确定LepRb（Gal）神经元在瘦素依赖性能量稳态调节中的贡献。我们将专门研究这些甘丙肽神经元中LepRb被破坏的小鼠的体重、食物摄入或能量消耗的任何扰动。因此，我们预期LepRbKO（Gal）小鼠是贪食和肥胖的。 2. 研究LepRb（Gal）神经元的调控。我们将使用报告小鼠来可视化LepRb（Gal）神经元，并定义LepRb（Gal）神经元的调节机制。我们将确定exPFA中的LepRb或LepRb（Gal）神经元是否受到瘦素或生理刺激如禁食和再喂养（通过cFos诱导和/或甘丙肽调节）的刺激，以及它们是否共表达抑制性递质GABA。我们将进一步研究ARC输入（如黑皮质素系统）对LepRb（Gal）神经元的调节作用，研究阻断或阻断ARC输入后LepRb（Gal）的调节作用。 3. 研究LepRb（Gal）神经元的神经解剖回路。我们将通过使用传统和新颖的追踪方法（在exPFA中LepRb或甘丙肽神经元特异性示踪剂表达）来定义LepRb（Gal）神经元（例如PVN）的轴突投射位点。此外，我们将通过使用exPFA中顺行或逆行跨突触示踪剂的LepRb或甘丙肽神经元特异性表达来鉴定由LepRb（Gal）神经元（例如在PVN中）支配或支配LepRb（Gal）神经元（例如来自ARC）的神经元。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Specific Aims We hypothesize that LepRb neurons in the extended perifornical area (exPFA), specifically LepRb(Gal) neurons, play a crucial role in mediating anorexigenic leptin actions via PVN outputs and thus control feeding behavior. Our overall goal is to understand the physiologic function and underlying neuronal network of LepRb(Gal) neurons as well as to investigate the overall population of LepRb neurons in the exPFA. We will thus: 1. Determine the role of LepRb(Gal) neurons in physiologic leptin action. We will examine the phenotype of mice with targeted deletion of LepRb in galanin neurons (LepRbKO(Gal) mice) to determine the contribution of LepRb(Gal) neurons in leptin dependent regulation of energy homeostasis. We will specifically investigate any perturbation in body weight, food intake or energy expenditure in these mice with disrupted LepRb in Galanin neurons. Thus, we expect LepRbKO(Gal) mice to be hyperphagic and obese. 2. Investigate the regulation of LepRb(Gal) neurons. We will use reporter mice to visualize LepRb(Gal) neurons immunohistochemically and define regulatory mechanisms of LepRb(Gal) neurons. We will determine if LepRb or LepRb(Gal) neurons in the exPFA are stimulated by leptin or physiological stimuli like fasting and refeeding (via cFos induction and/or regulation of galanin) and if they co-express the inhibitory transmitter GABA. We will further study the contribution of ARC inputs (e.g. melanocortin system) to regulate LepRb(Gal) neurons by investigating LepRb(Gal) regulation after blockade or ablation of ARC inputs. 3. Investigate the neuroanatomic circuits of LepRb(Gal) neurons. We will define axonal projection sites of LepRb(Gal) neurons (e.g. the PVN) by using traditional and novel tracing methods (LepRb or galanin neuron-specific tracer expression in the exPFA). Furthermore, we will identify the neurons that are innervated by LepRb(Gal) neurons (e.g. in the PVN) or that innervate LepRb(Gal) neurons (e.g. from the ARC), by using LepRb or galanin neuron-specific expression of anterograde or retrograde transsynaptic tracers in the exPFA.