NEURAL CONTROL OF MAGNOCELLULAR NEUROENDOCRINE CELLS

拟议工作的长期目标是了解控制 参与成年哺乳动物正常功能的机制 下丘脑 具体来说，这项工作的中心是大细胞 下丘脑-神经垂体系统神经内分泌细胞 (HNS)主要包括视上核和室旁核 (PVN)细胞核及其轴突投射。 跨国公司合成 催产素或加压素，并且响应于生理刺激， 这些肽来自垂体神经叶或垂体内的轴突末梢， CNS。 众所周知，在水调节、控制中发挥着重要作用 血压，生殖生理学和年轻人的护理， 模型系统产生了许多关于CNS功能的见解。 这么好 研究的是HNS输出的外围效应，即使是来自 SON和PVN的体外实验通常与以下直接相关： 完整动物的功能。 为了进一步加强中央 作为这项工作的使命，本建议侧重于HNS的两个主要方面 功能：跨国公司之间的相互作用，特别是 神经元间的耦合，以及调节 MNC兴奋性。 拟议的研究将使用电生理学 方法采用脑细胞内膜片钳记录技术 切片，伴随着免疫细胞化学和生物化学方法，所有 旨在揭示CNS功能的基本机制。 具体 目标是：目标1。 为了继续研究神经元间的 在SON中的耦合。 实验将进一步确定生理 增强或减弱耦合的条件， 在受体活化和偶联之间， 调节MNC偶联的机制。 目标2. 继续调查 确定生理变化改变MNC的机制 兴奋性 具体的研究将调查的贡献， 神经元组胺、催产素和MNC的内在离子机制 兴奋性，因此，机制，最终管理肽 release. 要调查的因素包括：去极化后， 电位、平台电位、受体介导的电导，以及 终止阶段性放电的爆发，以及 那个禽兽

Long-term goals of the proposed work are to understand controlling mechanisms involved in the normal functioning of the adult mammalian hypothalamus. Specifically, this work centers on the magnocellular neuroendocrine cells (MNCS) of the hpothalamo-neurohypophysial system (HNS), consisting chiefly of the supraoptic (SON) and paraventricular (PVN) nuclei and their axonal projections. MNCs synthesize either oxytocin or vasopressin and, in response to physiological stimuli, release these peptides from axon terminals in the pituitary neural lobe or within the CNS. Well known to play important roles in water regulation, control of blood pressure, reproductive physiology and care of the young, this model system has yielded many insights into CNS functioning. So well studied are the peripheral effects of HNS outputs that even results from in vitro experiments with the SON and PVN can often be related directly to the functioning of the intact animal. In order to further the central mission of this work, this proposal focuses on two main aspects of HNS functioning: interactions among the MNCs themselves, particularly interneuronal coupling, and extrinsic and intrinsic factors that modulate MNC excitability. The proposed studies will use electrophysiological methods, intracellular an patch-clamp recording techniques in brain slices, accompanied by immunocytochemical and biochemical approaches, all aimed at uncovering fundamental mechanisms of CNS functioning. Specific aims are: Aim 1. To continue our investigations of interneuronal coupling in the SON. Experiments will further define the physiological conditions that enhance or diminish coupling, define the relationships between receptor activation and coupling, and determine cellular mechanisms that modulate MNC coupling. Aim 2. To continue investigation determining the mechanisms by which physiological changes alter MNC excitability. Specific studies will investigate the contributions of neuronal histamine, oxytocin, and intrinsic ionic mechanisms to MNC excitability and, thus, to mechanisms ultimately governing peptide release. Factors to be investigated include: depolarizing after potentials, plateau potentials, receptor-mediated conductances, and termination of bursts of phasic firing, as well as physiological state of the animal.