HYPOTHALAMIC HYPOCRETIN PATHWAYS MODULATING FEEDING

外侧下丘脑（LH）具有历史作用， 大脑的“进食中心”虽然能源监管现在被认为是 更复杂的是，LH在食物摄入和体重调节中的作用 依然强大最近发现的hypocretins（也称为hypocretins）， 食欲素），Hcrt 1和Hcrt 2，似乎提供了一种手段，以扩大理解 LH及其在能量调节网络中的作用。Hcrts最近 确定了引起剂量依赖性进食的食欲神经肽 LH给药后，似乎与各种其他 重要的进食调节回路Hcrt受体广泛分布于 分布在整个大脑，并在几个关键的能量 监管场所。LH内的含Hcrt神经元投射并激活 其中几个网站。发现含有LH Hcrt的神经元 与其他参与食欲和体重调节的关键大脑部位， 我们认为，Hcrt刺激LH激活这些位点的发现， 至关重要。调查人员有经验探索的性质， 通过特定的神经调质连接的大脑部位之间的相互作用。的 现有数据表明，这种方法将非常有用， 确定LH和Hcrts如何适应能量调节网络， 有助于我们理解能量平衡和代谢 紊乱此外，如果受Hcrts影响的神经通路是 确定，然后可以探索这些途径的药理学改变。 待检验的总体假设如下：含有下丘脑泌素的神经元 源自LH的通路与其他摄食调节脑沟通 位点和神经调质以整合的方式调节进食。的 该项目的具体目标是定位Hcrt作用的具体位点 在LH中，通过检验其他指标，验证Hcrt在LH中的显著性 Hcrt摄食效应的区域（映射/摄食研究）;测量行为 和对LH Hcrt的反应引起的膳食模式（喂养/行为研究）; 建立Hcrt 1（cFos）摄食敏感性神经图谱 免疫组织化学、病变/进食研究）;确定氨基酸参与 在Hcrt 1诱导的摄食（GABA）/谷氨酸相互作用摄食研究中）;以及 确定LH Hcrt喂养信号和其他喂养信号之间的通信 相关的神经调质（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).