ULTRASTRUCTURE AND FUNCTION OF NERVE AND MUSCLE

本建议的目的是了解细胞和 各种神经肽调节活性的亚细胞机制 大脑神经元的数量 特别是，这些研究试图阐明 大脑神经元的功能和结构， 老年痴呆症 正是为了这个目的，校长 调查员（P.I.）发明了一种独特的方法 来自基底前脑核的神经元，包括基底核， 以及来自粗心点的去甲肾上腺素能神经元。 神经元 这些细胞核在阿尔茨海默病中会退化。 对培养的胆碱能神经元和去甲肾上腺素能神经元进行鉴定 采用免疫细胞化学和组织化学方法。 私家侦探计划 研究参与影响的信号转导过程， 神经肽对这些原代培养物的作用，特别强调 第二信使调节钾通道的机制。 那里 有三个主要项目： 第一个项目涉及内向整流K- 基底核和位点P物质和生长抑素通道 粗心的神经元 私家侦探之前的工作已经证明了 P通过抑制内向整流K-传导来兴奋神经元， 而生长抑素通过诱导类似的传导来抑制它们。 这 工作将在单通道层面上扩展，包括详细的 分析这些钾离子通道的特性。 第二个项目是确定第二信使。 私家侦探具有 发现两种不同的GTP结合蛋白似乎是第二种 P物质和生长抑素诱导的调节的信使， 钾电导 在这个项目中，P.I.建议审查 花生四烯酸代谢产物在生长抑素和物质中的作用 磷诱导的钾通道调节。 第三个项目是研究离子和第二信使机制 参与甘丙肽和神经降压素对培养细胞核的作用 采用全细胞钳夹和单细胞钳夹技术， 频道录制 试点研究的初步结果表明， 甘丙肽抑制了粗心神经元，而甘丙肽和 神经降压素兴奋基底核神经元。

The objective of this proposal is to understand the cellular and subcellular mechanisms by which various neuropeptides modulate the activity of brain neurons. Particularly, these studies attempt to elucidate the function and structure of brain neurons that are correlated with Alzheimer's disease. It was for this purpose that the principal investigator (P.I.) developed a unique method of culturing cholinergic neurons from the basal forebrain nuclei including the nucleus basalis as well as the noradrenergic neurons from the locus careless. Neurons in these nuclei have been shown to degenerate in Alzheimer's disease. Cultured cholinergic neurons and noradrenergic neurons were identified using immunocytochemical and histochemical methods. The P.I. plans to study the signal transduction process involved in the effects of neuropeptides on these primary cultures with particular emphasis on the mechanism by which second messengers modulate potassium channels. There are three major projects: The first project deals with the modulation of the inwardly rectifying K- channels by substance P and somatostatin in nucleus basalis and locus careless neurons. The P.I.'s previous work has demonstrated that substance P excites neurons by suppressing an inwardly rectifying K-conductance, whereas somatostatin inhibits them by inducing a similar conductance. This work will be extended at the single channel level to include a detailed analysis of the properties of these potassium channels. The second project is to identify the second messengers. The P.I. has found that two different GTP-binding proteins seem to be the second messengers for the substance P- and somatostatin-induced modulations of potassium conductance. In this project,the P.I. proposes to examine the role that arachidonic acid metabolites play in somatostatin- and substance P-induced modulation of potassium channels. The third project is to study the ionic and second messenger mechanisms involved in the effects of galanin and neurotensin on cultured nucleus basalis and locus careless neurons using the whole-cell clamp and single- channel recording. Preliminary results from the pilot study suggest that galanin inhibits locus careless neurons, whereas both galanin and neurotensin excite nucleus basalis neurons.