INTERNAL SENSING SYSTEMS IN HYPOTHALMUS

描述(申请人摘要)：本研究的长期目标 是：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) 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-还有 加压素产生系统在哺乳动物的大脑中普遍表达， 我们所学的知识应该在健康和健康方面具有普遍的适用性和重要性 疾病。2)确定所涉及的各种神经性和非神经性细胞类型 在由mHNS扮演的动态平衡角色中，并理解其过程 以及这些细胞类型相互作用的机制。主要由以下几部分组成 下丘脑视上核和室旁核及其主轴突 终止于垂体神经叶，mHNS已实现模型系统 状态，因为它具有良好的生理特性(例如，在水、血液中 压力和温度调节、分娩和哺乳/哺乳)和 在多个层次的分析的调查中揭示了许多信息。大家都知道 MHNS输出的外围效应即使是在 使用脑片或细胞进行生物物理和分子生物学研究 文化往往与完好无损的 系统。这里提出的工作包括利用显微镜， 免疫细胞化学、生化和生理方法的融合 旨在揭示中枢神经系统功能的基本机制的行动。特定的 所要求的支助期的目标如下：目标1.进一步 分析形态和化学变化的功能后果 伴随着mHNS的生理激活。具体的实验是 旨在确定涉及神经胶质影响的机制 神经垂体肽的释放及其在钙结合中的作用 蛋白质。目的2.调查新发现的蜂窝网络 似乎连接了脑膜、血管和实质神经胶质隔室，以及 它有可能成为下丘脑的信号系统，也许 在大脑的其他地方。特定的实验解决了细胞的问题 所涉及的类型，它们与细胞之间的通信模式 同型和异型的性质以及它们的信号能力。

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.