ELECTROPHYSIOLOGICAL CORRELATES OF VASOPRESSIN RELEASE

这个项目的广泛而长期的目标是促进理解 下丘脑的功能和形态组织 神经垂体系统，负责分泌 激素加压素（VP）和催产素（OT）。该方法是 多学科的，涉及1）相关的释放VP从神经 脑下垂体的叶，同时监测电活动 下丘脑大细胞神经分泌神经元; 2）形态学 和免疫化学鉴定的电生理特征 视上核（SON）神经元; 3）超微结构 识别由电刺激引起的神经垂体的变化 活动大部分工作是在一个模型系统上进行的， 视上神经垂体外植体，其中电生理和 延髓结节部神经元的神经分泌行为 可以分析视上核（SONT）。此外，一些 还将进行细胞内电生理学研究 在主要SON中，为了增加免疫化学的样品， 识别催产素神经元。 拟议研究期的具体目标是：1）继续 定量评估电活动之间的关系 完整的视上神经元和VP释放在更高的时间分辨率 2）检查是否确定VP和OT 神经元的光镜和电镜形态不同; 4） 检查VP和OT神经元是否可以通过电区分， 检查被动膜特性，尖峰频率依赖性变化， （尖峰增宽和超极化后电位），并在他们的 对神经递质、组胺和去甲肾上腺素的反应;以及5）对 确定尖峰脉冲的爆发是否引起内部的形态变化， 神经叶，以及任何此类变化对增加的依赖性 在已知导致细胞外钾或激素释放中 从爆发。 对下丘脑-神经垂体系统的研究提供了一种手段， 检查电活动和激素释放之间的关系， 以及它们的形态学相关物。因为据了解， 细胞，甚至本质上非神经元的细胞，当 释放激素，这些研究所回答的问题很可能是 适用于身体中的许多细胞类型。加压素尤其是 这对确定所有哺乳动物的适当水分平衡非常重要， 包括人类在内，其控制功能障碍导致许多病理性 条件，如尿崩症和慢性高钠血症。

The broad, long-term objective of this project is to advance understanding of the functional and morphological organization of the hypothalamo- neurohypophysial system, which is responsible for the secretion of the hormones vasopressin (VP) and oxytocin (OT). The approach is multidisciplinary and involves 1) correlating release of VP from the neural lobe of the pituitary gland while monitoring electrical activity of magnocellular neurosecretory neurons of the hypothalamus; 2) morphological and immunochemical identification of electrophysiologically characterized neurons in the supraoptic nucleus (SON); and 3) ultrastructural identification of changes in the neurohypophysis resulting from electrical activity. Much of the work is carried out on a model system, the rat supraoptico-neurohypophysial explant, wherein the electrophysiological and hormone-secreting behaviors of neurons in the tuberal portion of the supraoptic nucleus (SONt) can be analyzed. In addition, some of the intracellular electrophysiological investigations will also be carried out in the principal SON, in order to increase the sample of immunochemically identified oxytocin neurons. The specific aims for the proposed research period are: 1) to continue the quantitative assessment of the relationship between the electrical activity of intact supraoptic neurons and VP release at a higher temporal resolution than previously possible; 2) to examine whether identified VP and OT neurons differ in their light and electron microscopic morphology; 4) to examine whether VP and OT neurons can be distinguished electrically by examining passive membrane properties, spike frequency-dependent changes (spike broadening and hyperpolarizing afterpotential), and in their response to the neurotransmitters, histamine and noradrenaline; and 5) to determine whether a burst of spikes induces morphological changes within the neural lobe, and the dependence of any such changes upon the increase in extracellular potassium or hormone release which are known to result from the burst. Study of the hypothalamo-neurohypophysial system provides a means of examining the relationship between electrical activity and hormone release, as well as their morphological correlates. Since it is known that many cells, even non-neuronal in nature, also exhibit electrical activity when releasing hormones, the questions answered by these studies could well be applicable to many cell types in the body. Vasopressin in particular is very important in determining proper water balance in all mammals, including man, and dysfunctions in its control lead to many pathological conditions, such as diabetes insipidus and chronic hypernatremia.