IN VIVO DETECTION OF NEURONAL ACTIVITY

神经元活动的体内检测

• 批准号: 8171093
• 负责人: RUSSELL E JACOBS
• 金额: $ 101.22万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-01 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8171093
• 关键词: Anatomy; Atlases; Brain; Catechol O-Methyltransferase; Computer Retrieval of Information on Scientific Projects Database; Contrast Media; Data; Data Set; Detection; Diffusion Magnetic Resonance Imaging; Dopamine; Dopamine D2 Receptor; Drug abuse; Funding; Genotype; Grant; Image; Imaging Techniques; Injection of therapeutic agent; Institution; Knock-out; Limbic System; Location; Magnetic Resonance Imaging; Manganese; Maps; Methodology; Methods; Microscopic; Mus; Neurons; Neurotransmitters; Norepinephrine; Pathway interactions; Pharmaceutical Preparations; Phase; Research; Research Personnel; Resolution; Resources; Source; Specimen; Synapses; System; Three-dimensional analysis; United States National Institutes of Health; Weight; Work; in vivo; monoamine; mouse model; neuronal circuitry; research study; serotonin transporter; soft tissue; success; tool

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Microscopic Magnetic Resonance Imaging (mu MRI) provides in vivo three dimensional images of the mouse brain at high resolution (approximately 20 mu m) with exquisite soft tissue contrast. In this project we will combine Manganese Enhanced MRI (MEMRI) and Diffusion Tensor Imaging (DTI) to obtain precise maps of activated neuronal circuitry and anatomy in mouse models of importance in studies of drug abuse. Mn2+ acts as an effective MRI contrast agent that it is taken up by active neurons, retained, and passed along neuronal circuitry trans-synaptically. Specific circuits can be probed using focal stereotaxic injections of Mn2+ at different locations. Results obtained in our CEBRA Phase I work indicate that Mn2+ can be detected 3-5 synapses away from the point of injection. In this proposal we will: 1. Map normal neuronal pathways associated with the limbic system building on our Phase IR21 successes in combining T2 weighted, MEMRI, and DTI techniques. Correlate our combined methodology with traditional tract tracing methods. Apply quantitative tools for statistical analysis of 3D MR images using deformation fields and statistical parametric (and nonparametric) maps. These studies will provide a standard atlas of anatomy and activity upon which changes due to altered genotype can be mapped. The same maps will be of general use to map changes due to a myriad of other factors (e.g. drug treatment). 2. Compare and contrast the anatomy and activity of neuronal pathways in mouse models involving disruptions in monoamine neurotransmitters. We will map anatomy and activity with structural MRI, MEMRI, and DTI in: C57BL/6J mice to determine normal anatomy and activity; dopamine (DAT), norepinephrine (NET) and serotonin transporter (SERT) knockouts; dopamine D1 a and D2 receptor knockouts; catechol-O-methyltransferase (COMT) knockout. Experiments will involve recording high resolution three dimensional T2 weighted, DTI, and MEMRI in vivo and subsequently in fixed specimens; data transfer to a Network Accessible Storage system for facile access across the net; warping each data set to a common reference; and detailed statistical analyses of morphological and activity differences.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 显微磁共振成像 (mu MRI) 以高分辨率（约 20 μm）提供小鼠大脑的活体三维图像，并具有精美的软组织对比度。在这个项目中，我们将结合锰增强 MRI (MEMRI) 和扩散张量成像 (DTI)，以获得在药物滥用研究中具有重要意义的小鼠模型中激活的神经元回路和解剖结构的精确图。 Mn2+ 是一种有效的 MRI 造影剂，它被活跃的神经元吸收、保留并沿神经元回路跨突触传递。可以在不同位置使用 Mn2+ 局部立体定向注射来探测特定的电路。我们的 CEBRA 第一阶段工作获得的结果表明，可以在距注射点 3-5 个突触处检测到 Mn2+。在本提案中，我们将： 1. 建立在 IR21 阶段成功结合 T2 加权、MEMRI 和 DTI 技术的基础上，绘制与边缘系统相关的正常神经元通路。将我们的组合方法与传统的追踪方法相关联。使用变形场和统计参数（和非参数）图应用定量工具对 3D MR 图像进行统计分析。这些研究将提供一个标准的解剖学和活动图谱，可以根据该图谱绘制由于基因型改变而引起的变化。相同的地图将普遍用于绘制由于无数其他因素（例如药物治疗）而引起的变化。 2. 比较和对比涉及单胺神经递质破坏的小鼠模型中神经元通路的解剖结构和活性。我们将使用结构 MRI、MEMRI 和 DTI 绘制 C57BL/6J 小鼠的解剖结构和活动图，以确定正常的解剖结构和活动；多巴胺 (DAT)、去甲肾上腺素 (NET) 和血清素转运蛋白 (SERT) 敲除；多巴胺 D1a 和 D2 受体敲除；儿茶酚-O-甲基转移酶（COMT）敲除。实验将涉及在体内以及随后在固定样本中记录高分辨率三维 T2 加权、DTI 和 MEMRI；将数据传输到网络可访问存储系统，以便通过网络轻松访问；将每个数据集扭曲为公共参考；以及形态和活性差异的详细统计分析。