NEURAL CONTROL OF MAGNOCELLULAR NEUROENDOCRINE CELLS

拟议工作的长期目标是理解控制 成年哺乳动物正常功能的机制 下丘脑。具体地说，这项工作以巨细胞为中心 下丘脑-神经垂体系统的神经内分泌细胞 (HNS)，主要由视上核(SON)和室旁核组成 (PVN)核及其轴突投射。跨国公司可以合成任何一种 催产素或加压素，并对生理刺激作出反应，释放 这些肽来自于垂体神经叶内或内的轴突终末 中枢神经系统。众所周知，在水调控中发挥着重要作用 血压，生殖生理和照顾孩子，这一点 模型系统已经对中枢神经系统的功能产生了许多见解。太好了 研究的是HNS输出的外围效应，甚至结果来自 在体外实验中，SON和PVN经常直接相关 完整的动物的功能。为了进一步推动中央 这项工作的使命，这项建议侧重于HNS的两个主要方面 运作：跨国公司之间的相互作用，特别是 神经元间耦合，以及调节的外在和内在因素 跨国公司的兴奋性。拟议的研究将使用电生理学 方法：脑细胞内膜片钳记录技术 切片，伴随着免疫细胞化学和生化方法，都 旨在揭示中枢神经系统功能的基本机制。特定的 目标是：目标1.继续我们对神经元间的研究 在儿子的配合下。实验将进一步定义生理学 增强或减弱耦合的条件，定义关系 受体激活和偶联之间的关系，并决定细胞 调节跨国公司耦合的机制。目标2.继续调查 确定生理变化改变单核细胞的机制 兴奋性。具体研究将调查以下方面的贡献 神经元组胺、催产素和单核细胞的内在离子机制 兴奋性，从而影响最终支配多肽的机制 放手。需要调查的因素包括：去极化后 电位、平台电位、受体介导的电导和 终止相性放电的爆发，以及生理状态 这只动物。

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.