NEURAL CONTROL OF MAGNOCELLULAR NEUROENDOCRINE CELLS

目的是要了解与控制 巨细胞神经内分泌系统。普遍存在于哺乳动物物种中， 该系统在很大程度上负责制造和分发 催产素和加压素这两个已知的多肽对 外周组织(如乳腺、子宫和血管光滑 肌肉、肾脏和其他)。这些多肽也可以在 中枢性突触，扩大了它们的功能作用，包括神经- 递质/调节器以及神经内分泌作用。阿片类药物 强啡肽与加压素共同定位和释放 对控制这些神经元活动的因素的兴趣增强。在……里面 这种应用，特别注重下丘脑的主要部位 视上核(SON)和室旁核(PVN) 主要由大细胞系统组成。过去五年的工作 支持的重点是突触输入和非突触机制， 细胞-细胞相互作用和局部电路似乎参与了 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，由于此型号系统显示 真正显著的可塑性程度，取决于具体情况 生理需求。 所要求的支助期的具体目标是： 1.研究电性耦合的调制机制 在大细胞神经肽能神经元中。 2.为了进一步描述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 核团(组胺能)。 3.研究邻近局部环路神经元(如内侧)的作用 子巨细胞控制的杏仁核周围区) 神经元。 4.探讨生理性刺激对神经元兴奋性的影响。 与状态相关的变量，如性腺类固醇和渗透压。 这项工作将使用的方法包括：(A)细胞内 体外维持脑片神经元的记录和染色，(B) 记录和注射细胞的免疫细胞化学鉴定，(C) 递质/调节剂激动剂和拮抗剂的应用，(D) 控制大鼠的水合和生殖激素状态。

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.