Non-Homeostatic Neural Controls of Food Intake

新陈代谢和非新陈代谢共同决定了摄食行为的启动和维持 各种因素。在后者中，环境线索以及奖励、认知和情感因素起着重要作用 在现代世界中，特别是在人类食物摄入量方面，它发挥着重要作用。这些非动态平衡因素是 主要在皮质边缘结构中加工，如前额叶皮质、杏仁核和腹侧纹状体。 一个重要的问题是了解代谢和非代谢因素是如何以及在哪里整合在一起的 增加食物的摄入量。拟议的工作集中在这个问题的一个方面，通过研究解剖， 腹侧纹状体与下丘脑肽能神经元的神经化学和功能关系 与能量平衡的动态平衡调节有关的回路。 在目标1中，我们确定了下丘脑腹侧纹状体投射的靶点，这些投射与大量摄入 伏隔核或腹侧苍白球内的化学操作诱导的特定食物，使用 Fos表达、神经元示踪、免疫组织化学和原位杂交。在目标2中，我们假设 伏隔核中的化学操作刺激了更多的食物摄取，并超越了正常 通过作用于食欲和/或厌食的下丘脑信号来控制饱食大鼠的体内平衡 系统。我们通过使用选择性拮抗剂和激动剂的药理实验来测试这一点。 “喂食”多肽受体、解剖定位的免疫毒性损伤和小鼠基因敲除模型。在……里面 目的：我们假设腹侧纹状体D下丘脑投射在急性脑损伤中起重要作用。 对美味食物的高吞噬反应与长期暴露在肥胖中的关系 可口的饮食。为此，我们使用了两种不同的慢性病变模型，它们中断了 腹侧纹状体-下丘脑回路，并测量食物摄入量的“喜欢”和“想要”两个方面 如肥胖和体重。这些结果对于(1)获得详细的解剖学和 神经化学洞察奖赏和内环境平衡神经系统之间的关系，(2) 开发不同心理过程如何涉及食物的概念框架 奖赏是神经组织的，以及(3)药物和行为疗法的发展 在一个丰富多彩的世界里，对抗“常见”肥胖的工具。

The initiation and maintenance of ingestive behavior is co-determined by metabolic and non-metabolic factors. Among the latter, environmental cues as well as reward, cognitive and emotional factors play an important role, particularly in human food intake in the modern world. These non-homeostatic factors are processed mainly in cortico-limbic structures such as the prefrontal cortex, amygdala, and ventral striatum. An important issue is to understand how and where metabolic and non-metabolic factors are integrated to drive food intake. The proposed work focuses on one aspect of this issue by examining the anatomical, neurochemical, and functional relationship between the ventral striatum and the hypothalamic peptidergic circuits implicated in the homeostatic regulation of energy balance. In Aim 1, we identify hypothalamic targets of ventral striatal projections involved in the robust intake of specific foods induced by chemical manipulations within the nucleus accumbens or ventral pallidum, using Fos expression, neuronal tracing, immunohistochemistry, and in situ hybridization. In Aim 2 we hypothesize that chemical manipulations in the nucleus accumbens stimulate further food intake and override normal homeostatic controls in fully satiated rats by acting on orexigenic and/or anorexigenic hypothalamic signaling systems. We test this by using pharmacological experiments with selective antagonists and agonists against "feeding" peptide receptors, anatomically localized immunotoxic lesions, and murine knockout models. In Aim 3 we hypothesize that ventral striatum D hypothalamus projections play an important role in the acute hyperphagic response to palatable foods and in the development of obesity with chronic exposure to palatable diets. To this end, we use two different chronic lesion models that interrupt specific components of ventral striatal-hypothalamic circuitry, and measure both "liking" and "wanting" aspects of food intake as well as adiposity and body weight. The results will be important for (1) gaining detailed anatomical and neurochemical insight into the relationship between reward and homeostatic neural systems, (2) the development of a conceptual framework of how the different psychological processes involved in food reward are neurologically organized, and (3) the development of pharmacological and behavioral therapeutic tools to counteract "common" obesity in a world of plenty.