IN VIVO DETECTION OF NEURONAL ACTIVITY

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 显微磁共振成像（μ MRI）提供了高分辨率（约20 μ m）的小鼠大脑的体内三维图像与精致的软组织对比。在这个项目中，我们将结合联合收割机锰增强MRI（MEMRI）和扩散张量成像（DTI），以获得精确的地图激活的神经元回路和解剖在药物滥用研究的重要性小鼠模型。Mn 2+作为有效的MRI造影剂，其被活性神经元摄取、保留并沿沿着神经元回路跨突触传递。可以使用Mn 2+在不同位置的局灶性立体定位注射来探测特定电路。在我们的CEBRA第一阶段工作中获得的结果表明，Mn 2+可以在距离注射点3-5个突触处检测到。在本提案中，我们将：1。基于我们在IR 21阶段成功结合T2加权、MEMRI和DTI技术，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道追踪方法相关联。应用定量工具，使用变形场和统计参数（和非参数）图对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，在此基础上可以绘制由于基因型改变而引起的变化。同样的地图将普遍用于绘制由于无数其他因素（例如药物治疗）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和活性。我们将在以下小鼠中用结构MRI、MEMRI和DTI绘制解剖和活动图：C57 BL/6 J小鼠以确定正常解剖和活动;多巴胺（DAT）、去甲肾上腺素（NET）和5-羟色胺转运蛋白（SERT）敲除;多巴胺D1 α和D2受体敲除;儿茶酚-O-甲基转移酶（COMT）敲除。实验将涉及记录高分辨率三维T2加权，DTI和MEMRI在体内，随后在固定标本;数据传输到一个网络可扩展存储系统，方便访问整个网络;扭曲每个数据集的共同参考;和形态和活动差异的详细统计分析。

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.