HYPOTHALAMIC HYPOCRETIN PATHWAYS MODULATING FEEDING

外侧下丘脑(LH)在历史上的作用是 大脑的“喂养中心”。尽管能源监管现在已知是 更复杂的是，黄体生成素在食物摄入和体重调节中的作用 仍然很强大。最近发现的亚克汀类(也称为 食欲素)、Hcrt 1和Hcrt 2似乎提供了一种扩大理解的手段 黄体生成素及其在能源管理网络中的作用。HCRT是新成立的 鉴定出可引起剂量依赖摄食的食欲神经肽 在服用黄体生成素后，似乎与各种其他 重要的摄食调节回路。Hcrt受体广泛存在于 分布在整个大脑中，并在几个关键能量中发现 监管网站。黄体生成素内含hcrt的神经元投射并激活 有几个这样的网站。发现含促黄体生成素受体的神经元 与食欲和体重调节有关的其他关键大脑部位，以及 我们认为，Hcrt刺激促黄体生成素激活这些部位的发现是 至关重要。调查人员有调查性质的经验 通过特定的神经调节剂连接的大脑部位之间的相互作用。这个 现有数据表明，这种方法将在以下方面非常有用 确定LH和HCRT如何融入能源监管网络， 将有助于我们理解能量动态平衡和新陈代谢 精神错乱。此外，如果受HCRT影响的神经通路是 一旦确定，就可以探索这些通路的药理变化。 要检验的总体假设如下：含有神经的下丘脑克汀素 起源于黄体生成素的通路与其他摄食调节脑沟通 一种整合的方式来调节摄食的部位和神经调节剂。这个 该项目的具体目标是使HCRT行动的具体地点本地化 在LH内，通过测试其他参数验证HCRT在LH中的重要性 HCRT饲喂效果的区域(绘图/饲喂研究).测量行为 以及对LHCRT的反应引起的进食模式(喂养/行为研究)； 建立对Hcrt-1(CFos)摄食敏感性的神经图谱 免疫组织化学、损伤/喂养研究)；确定氨基酸参与 在Hcrt 1诱导摄食(GABA)/谷氨酸相互作用摄食研究中)；以及 确定LHCRT饲喂信号与其他饲喂信号之间的通信 相关神经调节剂(相互作用喂养研究)。

The lateral hypothalamus (LH) has a historical role as the "feeding center" of the brain. Although energy regulation is now known to be more complex, the role of the LH in food intake and body weight regulation remains strong. The recent discovery of the hypocretins (also known as orexins), Hcrt 1 and Hcrt 2, appears to provide a means to expand understanding of the LH and its role in the energy regulatory network. The Hcrts are newly identified orexigenic neuropeptides that elicit dose-dependent feeding following LH administration, and appear to interact with a variety of other important feeding-regulatory circuits. The Hcrt receptors are widely distributed throughout the brain, and are found in several key energy regulatory sites. Hcrt-containing neurons within the LH project to and activate several of these sites. The finding that LH Hcrt-containing neurons communicate with other key brain sites involved in appetite and body weight regulation, and the finding that Hcrt stimulation of LH activates those sites is, we think, of critical importance. The investigators have experience probing the nature of interactions between brain sites connected by specific neuromodulators. The existing data indicates that such an approach will be very useful in determining how the LH and the Hcrts fit into the energy regulatory network, and will aid in our understanding of energy homeostasis and metabolic disorders. Further, if the neural pathways influenced by the Hcrts are determined, then pharmacological alteration of these pathways can be explored. The overall hypothesis to be tested is as follows: hypocretin containing neural pathways originating in the LH communicate with other feeding regulatory brain sites and neuromodulators in an integrated fashion to modulate feeding. The specific aims of this project are to localize the specific site of Hcrt action within the LH, verify the significance of Hcrt in the LH by testing other regions for Hcrt feeding effects (mapping/feeding studies); measure behaviors and meal patterns elicited in response to LH Hcrt (feeding/behavioral studies); develop the neural map of feeding sensitivity to Hcrt 1 (cFos immunohistochemistry, lesion/feeding studies); determine amino acid involvement in Hcrt 1 induced feeding (GABA)/glutamate interaction feeding studies); and determine communication between LH Hcrt feeding signals and other feeding related neuromodulators (interaction feeding studies).