CLASSIFICATION OF NICOTINIC ACETYLCHOLINE RECEPTORS IN NEURONS

神经元烟碱乙酰胆碱受体的分类

• 批准号: 6112662
• 负责人: Gerald D Fischbach
• 金额: $ 19.78万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-12-01 至 1999-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6112662
• 关键词: evoked potentials; laboratory mouse; neural transmission; neurons; neuroregulation; neurotrophic factors; nicotinic receptors; receptor expression; tissue /cell culture

The main goal of this project is to study the regulation of nicotinic acetylcholine receptors (nAChRs) in the CNS by neuregulins, a new family of neurotrophic factors that are present in cholinergic neurons throughout central and peripheral nervous system. We will also determine if neuregulin induced change in the number of distribution of functional nAChRs alters synaptic transmission in the circuits described. Neuregulins will be studied in vitro by adding them to neuronal cell cultures, and they will be studied in vivo in mutant mice that exhibit diminished neuregulin expression. To maximize the generality of our results, we will study neurons dissociated from the Medial Habenula (MHb), the Interpeduncular Nucleus (IPN), the Substantia Nigra, (SN), and the Ventral Tegmental Area (VTA). Each region offers advantages for studies of nAChR regulation. In each case, the nuclei can be dissected easily from embryos and neonatal animals, the cells can be maintained in spars cell culture, a subpopulation of the neurons receive cholinergic synaptic inputs, and the neurons express a diverse array of nAChRs. In vitro cell culture experiments are described in the three Specific Aims. In vivo studies that utilize fresh slices prepared from normal and mutant mice are described in Collaborations. We emphasize microelectrode recordings of ACh induced currents because we want to study regulation of functional receptors. However, ligand binding and receptor subunit gene expression will be used to confirm and extend results in some cases. In each series of experiments, we will begin with the relatively well studied MHb-IPN system, but results will be extended to Septal-MHb, and PPT-SN/VTA interactions.

该项目的主要目标是研究烟碱的调节 神经蛋白的乙酰胆碱受体（NACHRS）是新家族的神经蛋白 整个胆碱能神经元中存在的神经营养因素 中央和周围神经系统。我们还将确定是否 神经调节蛋白诱导的功能分布次数变化 NACHRS改变了所描述的电路中的突触传播。神经结合蛋白 将通过将它们添加到神经元细胞培养物中，并在体外研究 它们将在突变小鼠中的体内研究 神经调节蛋白的表达。 为了最大程度地提高结果的普遍性，我们将研究神经元 与内侧Habenula（MHB）分离，枝条核 （ipn），底底，（sn）和腹侧对段区域（VTA）。 每个区域为NACHR调节研究提供了优势。每个 情况，可以轻松地从胚胎和新生儿中剖析核 动物，细胞可以维持在Spars Cell培养中，A 神经元的亚群接受胆碱能突触输入，并接受 神经元表达各种各样的nACHR。体外细胞培养 实验在三个特定目标中描述。体内研究 利用从正常小鼠和突变小鼠制备的新鲜切片在 协作。我们强调ACH诱导的微电极记录 电流是因为我们想研究功能受体的调节。 但是，将使用配体结合和受体亚基基因表达 在某些情况下确认和扩展结果。在每个系列中 实验，我们将从研究相对良好的MHB-IPN开始 系统，但结果将扩展到分隔MHB和PPT-SN/VTA 互动。