权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Invivoパッチクランプ法を用いた線条体シナプス伝達機構の解析

体内膜片钳法分析纹状体突触传递机制

基本信息

批准号：
17500281
负责人：
MOMIYAMA Toshihiko
金额：
$ 2.3万
依托单位：
National Institute for Physiological Sciences
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

项目摘要

Whole-cell patch-clamp recordings were carried out from neurons in the striatum and basal forebrain nuclei (BF). Membrane properties and profiles of synaptic transmission as well as its modulation were analyzed in various types of neurons.I) Cholinergic neurons in the rat BF were morphologically identified with the antibody for the receptor of a neurotrophic factor. This method enabled the real time identification of cholinergic neurons under the fluorescent microscope in the patch-clamp experiment, enhancing the efficiency of the experiments.1) Non-NMDA glutamatergic excitatory postsynaptic currents (EPSCs) and GABAergic inhibitory postsynaptic currents (IPSCs) were recorded in BF cholinergic neurons and modulation of these EPSCs and IPSCs by somatostatin was analyzed. The study has clarified that EPSCs and IPSCs were presynaptically inhibited by activation of different sst receptors (Momiyama ＆ Zaborszky, 2006).2) The mechanisms underlying dopamine-receptor-mediated inhibition of the EPSCs evoked in BF cholinergic neurons were analyzed. The study has shown that selective coupling between dopamine D1-like receptors and P/Q-type calcium channels for glutamate release (Momiyama ＆ Fukazawa, 2007).II) Analyses using dopamine receptor knock out mice have revealed that dopamine D2-like receptors are involved in the frequently-dependent suppression of GABA release onto cholinergic interneurons in the striatum (Momiyama ＆ Fukazawa, 2007).III) Abnormal behaviors were ameliorated in the Parkinson's disease model rats by grafting neuroepithelial stem cells of rats or swine, and morphological and electrophysiological studies have demonstrated that grafted cells survived in the host striatum to differentiate into functionally active neurons (in preparation).

全细胞膜片钳记录进行了纹状体和基底前脑核（BF）的神经元。膜的特性和配置文件的突触传递，以及其调制进行了分析，在各种类型的neurons.I）胆碱能神经元在大鼠BF的形态学鉴定与抗体的受体的神经营养因子。该方法可在荧光显微镜下真实的实时识别膜片钳实验中的胆碱能神经元，提高了实验效率。1）记录BF胆碱能神经元的非NMDA能兴奋性突触后电流（EPSC）和GABA能抑制性突触后电流（IPSC），并分析生长抑素对这些EPSC和IPSC的调节作用。该研究阐明了EPSC和IPSC通过激活不同的sst受体而被突触前抑制（Momiyama & Zaborszky，2006）。2）分析了多巴胺受体介导的对BF胆碱能神经元中诱发的EPSC的抑制的潜在机制。研究表明，多巴胺D1样受体和P/Q型钙通道之间选择性偶联谷氨酸释放II）使用多巴胺受体敲除小鼠的分析揭示了多巴胺D2样受体参与GABA释放到纹状体中胆碱能中间神经元上的频率依赖性抑制III）通过移植大鼠或猪的神经上皮干细胞，帕金森病模型大鼠的异常行为得到改善，并且形态学和电生理学研究已经证明，移植的细胞在宿主纹状体中存活以分化成功能活性神经元（制备中）。