NEUROPEPTIDES AND THEIR PHYSIOLOGICAL CONTROL

该项目的长期目标是识别传入信令 边缘前脑的机制、细胞反应和地形图 帮助调节老鼠体内动态平衡的神经回路。这一部分 前脑对调节行为、自主神经和 动物对动态平衡紊乱的内分泌反应。中环 假说是动态平衡紊乱改变了化学编码 通过调制编码的mRNAs来传递神经元内包含的信息 单一和共表达的神经肽。这些特定于细胞和刺激的 修饰促进了动物的适当反应，或者通过 调节自主神经系统、神经内分泌的活动 函数，或者可能通过修改中央图案生成器来实现 发展和规范目标导向的行为。因为这位亲戚 基础生理和行为的简单性以及 广泛的文献资料，该项目集中在调查 控制流体平衡的回路和机构的组织 那只老鼠。使用了两个实验模型：1)细胞脱水 由盐负荷提供；和2)，由 等渗体积耗竭。将结果与重要和良好联系起来 有文档记录的模型允许在令人信服的 语境框架不可能与许多其他当前使用的“压力”一起使用 模特们。所使用的检测方法-主要是在情景杂交和 免疫细胞化学-允许检测mRNAs和它们的变化 大鼠解剖区域和细胞类型中的同源肽 下丘脑和杏仁核对这两个截然不同但又相关的反应 刺激物。该提案将调查发射机和信号 修饰多肽基因表达的转导机制。 类似地，它解决了皮质酮通过 调节多肽基因表达可能由动物决定 生理状态。它将开始研究边缘前脑是如何 可能会集成来自多个刺激的输入，以制定适当的 回应。最后，该提案将涉及一些地形方面的问题 通过观察多肽(而不是信使核糖核酸)的反应来调节回路，以及 多肽受体mRNAs在大鼠局灶性脑损伤中的行为及可能意义 施加2种脱水刺激。从长远来看，调查 在电路调节内运行的地形和机制 动态平衡将提供一个框架来解决许多临床 精神障碍(如高血压、肥胖症、饮食失调)目前 对人类健康的核心重要性，扰乱了体内平衡 监管是其病因的核心。

The long-term goal of this project is to identify the afferent signalling mechanisms, cellular responses, and topography of the limbic forebrain neural circuits that help regulate homeostasis in the rat. This portion of the forebrain is critical for regulating the behavioral, autonomic and endocrine response of the animal to homeostatic disturbance. The central hypothesis is that homeostatic disturbances modify chemically-coded information contained within neurons by modulating the mRNAs that code for singly- and co-expressed neuropeptides. These cell- and stimulus-specific modifications facilitate the appropriate response by the animal, either by modulating the activity of the autonomic nervous system, neuroendocrine function, or perhaps by modifying the central pattern generators that develop and regulate goal-directed behaviors. Because of the relative simplicity of the underlying physiology and behavior along with an extensive literature, the project concentrates on investigating the organization of the circuits and mechanisms controlling fluid balance in the rat. Two experimental models are used; 1), cellular dehydration provided by salt-loading; and 2), extracellular dehydration provided by iso-osmotic volume depletion. Relating the results to important and well documented models allows the interpretation of data within a compelling and contextual framework not possible with many other currently used 'stress' models. The assay methods used-principally in situhybridization and immunocytochemistry-allows the detection of changes in mRNAs and their cognate peptides in anatomically defined regions and cell types of the rat hypothalamus and amygdala in response to these two distinct, but related stimuli. This proposal will investigate the transmitter and signal transduction mechanisms underlying modified peptide gene expression. Similarly, it addresses the possibility that the way corticosterone regulates peptide gene expression may be determined by the animals physiological status. It will begin investigating how the limbic forebrain might integrate inputs from multiple stimuli to formulate an appropriate response. Finally, the proposal will address some topographical aspects of the circuits by looking at peptide (rather that mRNA) responses, and the behavior and possible significance of peptide receptor mRNAs during the imposition of the 2 dehydration stimuli. In the long term, investigating the topography and mechanisms operating within the circuits regulating homeostasis will provide a framework for addressing many of the clinical disorders (eg. hypertension, obesity, eating disorders) currently of central importance to human health, that have perturbed homeostatic regulation at the core of their etiology.