Amylin receptors in the lateral dorsal tegmental area regulate food intake

 描述（由申请方提供）：胰淀素是一种胰源性激素，作用于CNS以减少食物摄入。虽然历史上胰淀素的低吞噬作用已被归因于最后区的处理，最近腹侧被盖区（VTA），中脑边缘奖励系统中的一个核，被强调为胰淀素介导的能量平衡和食物奖励的控制的神经和生理相关的行动网站。这些发现鼓励更广泛地评估中枢神经系统介导胰淀素对食物摄入和奖励的影响。鉴于脑干的外侧背侧被盖区（LDTg）：[1]接收来自后脑和前脑的进食相关核团的输入，[2]结合胰淀素，[3]将输入发送到VTA以调节奖励行为，所提出的目的将测试LDTg中的胰淀素受体信号传导对于能量平衡和食物奖励的调节是不可或缺的假设。具体而言，我们将测试LDTg胰淀素受体信号传导在调节能量平衡中的生理需求、LDTg胰淀素受体信号传导在食物的奖励价值中的作用以及与肠-脑胰高血糖素样肽-I（GLP-1）餐内饱足信号传导的潜在相互作用作为促进摄入抑制的推定机制。共同提出的目标将突出胰淀素受体系统，以及LDTg神经处理的食物摄入量和食物动机的行为的调节至关重要。

 DESCRIPTION (provided by applicant): Amylin is a pancreatic-derived hormone that acts in the CNS to reduce food intake. While historically the hypophagic effects of amylin have been attributed to processing by the area postrema, recently the ventral tegmental area (VTA), a nucleus in the mesolimbic reward system, was highlighted as a pharmacologically and physiologically relevant site of action for amylin-mediated control of energy balance and food reward. These discoveries encourage a broader assessment of the CNS circuitry mediating amylin's effects on food intake and reward. Given that the lateral dorsal tegmental area (LDTg) of the brainstem: [1] receives input from feeding-relevant nuclei of the hindbrain and forebrain, [2] binds amylin, and [3] sends input to the VTA to modulate rewarding behavior, the proposed aims will test the hypothesis that amylin receptor signaling in the LDTg is integral for the regulation of energy balance and food reward. Specifically, we will test the physiological requirement of LDTg amylin receptor signaling in regulation of energy balance, the role of LDTg amylin receptor signaling in rewarding value of food, and the potential interaction with gut-to-brain glucagon- like peptide-1 (GLP-1) within-meal satiation signaling as a putative mechanism contributing to intake suppression. Together the proposed aims will highlight the amylin receptor system, as well as LDTg neural processing as critical to the regulation of food intake and food motivated behaviors.