ELECTROPHYSIOLOGICAL CORRELATES OF VASOPRESSIN RELEASE

该项目广泛、长期的目标是推动 对细胞的功能和形态组织的理解 下丘脑-神经垂体系统，负责 荷尔蒙加压素和催产素的分泌。该系统是 用视上神经垂体外植体进行的初步体外研究 因为在这种情况下稳定的细胞内记录是可能的 由于膜的性质和神经递质的作用 更容易研究对细胞外的控制水平 流体。本项目将在很大程度上集中于对 在形态、膜性能等方面的异同 和神经递质反应性已确定的催产素和 雄性和雌性大鼠视上核内的加压素神经元 根据细胞内记录和填充确定，然后 免疫细胞化学鉴定。一般的假设是 催产素和加压素神经元具有不同的特征 除了它们的多肽表型，这是它们的基础或促进它们 在荷尔蒙释放过程中表达特定的激发模式的能力。一些人 差异可能是性别相关的，或者在女性身上，选择性地表现出来 在哺乳期，赋予这些神经元一种功能 可塑性，以适应激素分泌的需求。该项目还 涉及到确定大脑皮质核周区域的神经元 视上核充当中间神经元并提供抑制性突触 神经分泌神经元的输入。建议的具体目标是 研究期为：1)继续进行人物刻画 经鉴定的电生理和形态特征 催产素和加压素神经元，目的是了解为什么一些 属性是共享的，而其他属性不在这两类 神经分泌细胞；2)确定神经分泌细胞 神经调节剂组胺选择性地去极化细胞膜和 增强后叶加压素的去极化后电位，但不能增强催产素 神经元；3)确定GABA介导的性质和重要性 催产素和加压素神经元上的突触活动。加压素是 在确定所有哺乳动物的适当水分平衡方面非常重要， 包括人类在内，其控制功能障碍导致许多病理性 情况，如尿崩症和慢性高钠血症。一个 对催产素神经元活性控制机制的理解是 对了解这种激素有重要意义；S在女性体内的作用 哺乳和分娩，以及对其不太了解的男性。

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 and oxytocin. The system is studied primarily in vitro using a supraoptico-neurohypophysial explant from rats because stable intracellular recording are possible in this preparation, and because membrane properties and neurotransmitter actions are more easily studied with level of control over the extracellular fluid. This project will focus in large part on a detailed analysis of the similarities and differences in the morphology, membrane properties and neurotransmitter responsiveness of identified oxytocin and vasopressin neurons within the supraoptic nucleus in male and female rats as determined from intracellular recording and filling followed by immunocytochemical identification. The general hypothesis is that oxytocin and vasopressin neurons have distinguishable characteristics beyond their peptidergic phenotype, which underlie or facilitate their ability to express specific firing patterns during hormone release. Some differences may be sex-dependent, or in females, expressed selectively during the state of lactation, endowing these neurons with a functional plasticity to fit the demands of hormone secretion. The project also involves determining whether neurons in eh perinuclear zone of the supraoptic nucleus behave as interneurons and provide inhibitory synaptic inputs to neurosecretory neurons. The specific aims for the proposed research period are: 1) To continue the characterization of electrophysiological and morphological characteristics of identified oxytocin and vasopressin neurons, with the goal of understanding why some properties are shared and others are not between these two classes of neurosecretory cell; 2) To determine the mechanism by which the neuromodulator histamine selectively depolarizes the membrane and enhances the depolarizing afterpotential in vasopressin, but not oxytocin neurons; 3) To determine the nature and importance of GABA-mediated synaptic activity on oxytocin and vasopressin neurons. Vasopressin 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. An understanding of the mechanisms controlling oxytocin neuron activity are important to the understanding of this hormone;s role in females during lactation and labor, and to its ill-understood in males.