In Vivo Detection of Neuronal Activity

描述（申请人提供）：显微磁共振成像（mu MRI）提供高分辨率（约20 μ m）的小鼠大脑体内三维图像，具有精细的软组织对比度。在这个项目中，我们将结合锰增强MRI （MEMRI）和弥散张量成像（DTI）来获得在药物滥用研究中重要的小鼠模型中激活的神经元回路和解剖的精确地图。Mn2+作为一种有效的MRI造影剂，它被活跃的神经元吸收，保留，并沿神经元回路经突触传递。通过在不同位置定向注射Mn2+，可以探测特定的电路。我们在CEBRA I期研究中获得的结果表明，Mn2+可以在距离注射点3-5个突触处被检测到。在本提案中，我们将：在IR21期成功结合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。将我们的联合方法与传统的呼吸道追踪方法联系起来。应用定量工具，利用变形场和统计参数（和非参数）地图对3D磁共振图像进行统计分析。这些研究将提供一个标准的解剖和活动图谱，在这个图谱上，由于基因型改变而产生的变化可以被绘制出来。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）而引起的变化。2. 比较和对比小鼠模型中涉及单胺类神经递质中断的神经元通路的解剖结构和活动。我们将用结构MRI、MEMRI和DTI绘制C57BL/6J小鼠的解剖和活动图，以确定正常的解剖和活动；多巴胺（DAT）、去甲肾上腺素（NET）和血清素转运体（SERT）基因缺失；多巴胺D1 a和D2受体敲除；儿茶酚o -甲基转移酶（COMT）敲除。实验将包括在体内和随后的固定标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，以便在网络上方便地访问；将每个数据集扭曲为一个公共引用；并对形态和活性差异进行了详细的统计分析。

DESCRIPTION (provided by applicant): 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. .