NEUROPEPTIDES AND THEIR PHYSIOLOGICAL CONTROL

这个项目的长期目标是确定传入信号 边缘前脑的机制、细胞反应和地形图 帮助调节大鼠体内平衡的神经回路。 的该部分 前脑对于调节行为、自主神经和 动物对体内平衡紊乱的内分泌反应。 中央 一种假说认为，体内平衡紊乱会改变化学编码 神经元内包含的信息，通过调节编码 单独表达和共表达的神经肽。 这些细胞和刺激特异性 修饰促进动物的适当反应， 调节自主神经系统、神经内分泌 函数，或者可能通过修改中央模式生成器， 发展和规范目标导向的行为。 因为相对 简单的基本生理和行为沿着 广泛的文献，该项目集中在调查 控制流体平衡的回路和机构的组织 老鼠 采用了两种实验模型：1）细胞脱水 由盐负载提供;和2）由盐负载提供的细胞外脱水， 等渗容量耗竭。 将结果与重要和良好的 文档化的模型允许在一个令人信服的， 上下文框架不可能与许多其他目前使用的'压力' 模型 使用的测定方法-主要是原位杂交和 免疫细胞化学-允许检测mRNA及其 大鼠解剖学上确定的区域和细胞类型中的同源肽 下丘脑和杏仁核对这两种不同但相关的反应 刺激。 本提案将调查发射机和信号 修饰肽基因表达的转导机制。 同样，它也指出了皮质酮 调节肽基因表达的基因可以由动物决定 生理状态 它将开始研究边缘前脑 可以整合来自多个刺激的输入，以制定适当的 反应 最后，该提案将解决一些地形方面的问题， 通过观察肽（而不是mRNA）的反应， 肽受体mRNAs的行为和可能的意义 施加2种脱水刺激。 从长远来看，调查 电路内的地形和机制调节 稳态将提供一个框架，解决许多临床 疾病（例如，高血压、肥胖症、饮食失调）， 对人类健康至关重要， 调节是其病因学的核心。

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.