INTERNAL SENSING SYSTEMS IN HYPOTHALMUS

描述（申请人摘要）：本研究的长期目标 （1）了解哺乳动物的功能和控制 大细胞下丘脑神经垂体系统（mHNS），因为它的感觉和 对动物生理状态的变化做出反应，包括波动 在内部和外部环境中。因为这种催产素 加压素产生系统在哺乳动物脑中普遍表达， 我们所学的知识应该具有普遍的适用性和重要性， 疾病2)来识别不同的细胞类型，神经和非神经， 在mHNS发挥的稳态作用，并了解过程 以及这些细胞类型相互作用的机制。主要由 下丘脑视上核和室旁核及其主要轴突 终止在垂体神经叶，mHNS已实现模型系统 状态，因为它在生理上得到了很好的表征（例如，在水里，血里 压力和温度调节、分娩和哺乳/哺乳）， 在多个层面的调查分析中揭示了很多问题。众所周知， mHNS输出的外周效应，即使在 使用脑切片或细胞的生物物理学和分子生物学研究 文化往往与完整的社会功能有着有意义的联系。 系统这里提出的工作包括使用显微镜， 免疫细胞化学、生物化学和生理学的方法， 旨在揭示中枢神经系统功能的基本机制的手术。具体 在请求的支助期间，目标如下：目标1。进一步 分析形态和化学变化的功能后果， 伴随mHNS的生理激活。具体实验有 旨在确定神经胶质细胞影响 神经垂体肽释放，并在钙结合所发挥的作用 proteins.目标二。为了研究新发现的蜂窝网络， 似乎连接脑膜、血管和实质胶质室， 它有可能成为下丘脑的信号系统， 在大脑的其他地方。具体的实验解决了细胞的问题 涉及的类型，它们与细胞的细胞间通讯模式， 同型和异型性质以及它们的信号传导能力。

DESCRIPTION (applicant's abstract): The long term objectives of this research are: 1) to understand the functioning and control of the mammalian magnocellular hypothalamo-neurohypophysial system (mHNS) as it senses and responds to changes in the animal's physiological state, including fluctuations in both the internal and external milieu. Since this oxytocin- and vasopressin-producing system is ubiquitously expressed in mammalian brains, what we learn should have general applicability and importance in health and disease. 2) to identify the various cell types, neural and non-neural, involved in the homeostatic roles played by the mHNS, and to understand the processes and mechanisms by which these cell types interact. Consisting chiefly of the supraoptic and paraventricular nuclei of the hypothalamus and their main axonal terminations in the pituitary neural lobe, the mHNS has achieved model system status because it is well characterized physiologically (e.g., in water, blood pressure and temperature regulation, parturition and lactation/nursing) and has revealed much in investigations at many levels of analysis. So well known are the peripheral effects of mHNS outputs that even findings obtained in biophysical and molecular biological investigations using brain slices or cell cultures can most often be meaningfully related to functioning of the intact system. The work proposed here includes studies of the mHNS using microscopic, immunocytochemical, biochemical and physiological approaches as converging operations aimed at uncovering fundamental mechanisms of CNS function. Specific aims for the requested period of support are the following: Aim 1. To further analyze the functional consequences of morphological and chemical changes that accompany physiological activation of the mHNS. Specific experiments are directed at determining mechanisms involved in glial influences on neurohypophysial peptide release, and at the roles played by calcium binding proteins. Aim 2. To investigate the newly discovered cellular network that appears to link the meningeal, vascular and parenchymal glial compartments, and that has the potential to be a signaling system in the hypothalamus and perhaps elsewhere in the brain. Specific experiments address questions of the cell types involved, their modes of intercellular communication with cells of homotypic and heterotypic nature, and their signaling capacity.