NEURAL CONTROL OF MAGNOCELLULAR NEUROENDOCRINE CELLS

目的是了解参与控制的机制， 大细胞神经内分泌系统 在哺乳动物中普遍存在， 该系统主要负责制造和分销 肽催产素和血管加压素具有众所周知的作用， 外周组织（如乳腺、子宫和血管平滑肌 肌肉、肾脏和其他）。 这些肽也被发现在 中央突触，扩大其功能作用，包括神经元， 递质/调节剂以及神经内分泌作用。 阿片类药物 肽强啡肽与加压素共定位和共释放， 增强了对控制这些神经元活动的因素的兴趣。 在 在这种应用中，特别注意主要的下丘脑 视上核和室旁核， 主要包括巨细胞系统。 过去五年的工作 的支持集中在突触输入和非突触机制， 细胞间的相互作用和局部回路似乎参与了 控制该系统的兴奋性、激活和失活， 各种生理条件。 这一做法将继续下去。 在请求支持期间，由于该模型系统显示 真正显著的可塑性程度，取决于具体的 生理需求。 所要求的支助期的具体目标是： 1. 研究电耦合调制的机制 在大细胞神经肽能神经元中。 2. 为了进一步表征这些神经元的直接突触输入， 嗅球（兴奋性氨基酸介导）和结节乳头 核（组胺能）。 3. 为了研究附近的局部回路神经元（例如内侧 杏仁核，核周区）控制SON大细胞 神经元 4. 探讨生理性刺激对神经元兴奋性的影响， 状态相关变量，如性腺类固醇和渗透压。 在这项工作中使用的方法包括：（a）细胞内 记录和染色体外保存的脑切片中的神经元，（B） 记录和注射细胞的免疫细胞化学鉴定，（c） 传递剂/调节剂激动剂和拮抗剂的应用，（d） 大鼠的水合和生殖激素状态的操作。

Objectives are to understand the mechanisms involved in the control of the magnocellular neuroendocrine system. Ubiquitous among mammalian species, this system is largely responsible for the manufacture and distribution of the peptides oxytocin and vasopressin which have well-known actions on peripheral tissues (e.g. mammary glands, uterine and vascular smooth muscle, kidneys and others). These peptides have also been found at central synapses, broadening their functional role to include neuro- transmitter /modulator as well as neuroendocrine actions. That the opioid peptide dynorphin is co-localized and co-released with vasopressin has enhanced interest in factors controlling the activity of these neurons. In this application, special attention is paid to the major hypothalamic nuclei, the supra- optic (SON) and paraventricular (PVN) nuclei, that chiefly comprise the magnocellular system. Work over the past five years of support has focused on synaptic inputs and non-synaptic mechanisms, cell-cell interactions and local circuits that appear to be involved in controlling excitability, activation and inactivation of this system under a variety of physiological conditions. This approach will be continued during the period of requested support, since this model system displays a truly remarkable degree of plasticity, depending upon specific physiological demands. Specific aims for the requested period of support are: 1. To investigate mechanisms involved in modulation of electrical coupling among magnocellular neuropeptidergic neurons. 2. To further characterize the direct synaptic inputs to these neuron from olfactory bulbs (excitatory amino acid-mediated) and tuberomammillary nuclei (histaminergic). 3. To investigate the roles of nearby local circuit neurons (e.g. medial amygdaloid, perinuclear zone) in the control of the SON magnocellular neurons. 4. To investigate the influences on neuronal excitability of physiological state-related variables, such as gonadal steroids and osmotic pressure. The methodology to be used in this work includes: (a) intracellular recording and staining of neurons in brain slices maintained in vitro, (b) immunocytochemical identification of recorded and injected cells, (c) application of transmitter/modulator agonists and antagonists, (d) manipulations of the hydrational and reproductive hormonal states of rats.