IN VIVO DETECTION OF NEURONAL ACTIVITY

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 显微核磁共振成像(MU MRI)提供了具有精细软组织对比度的高分辨率(约20微米)的活体小鼠脑三维图像。在这个项目中，我们将结合锰增强磁共振成像(MEMRI)和扩散张量成像(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电路和解剖学的精确图谱。MN_2是一种有效的MRI造影剂，它被活跃的神经元摄取、保留并跨突触传递到神经元回路。通过在不同位置注射Mn2，可以探测特定的回路。我们在CEBRA一期工作中所获得的结果表明，在距离注入点3-5个突触的地方可以检测到Mn2。在这项建议中，我们将：1.在我们的IR21相上绘制与边缘系统相关的正常神经元路径图，成功地结合了T2加权、MEMRI和DTI技术。将我们的组合方法与传统的轨迹追踪方法相关联。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和活动图谱，在此基础上可以绘制由于基因改变而发生的变化。同样的地图将普遍用于地图因各种其他因素(如药物治疗)而发生的变化。2.比较和对比单胺类神经递质受阻的小鼠模型中神经元通路的解剖和活性。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5-羟色胺转运体(SERT)基因敲除；多巴胺D1a和D2受体基因敲除；儿茶酚-O-甲基转移酶(COMT)基因敲除。实验将包括在活体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于跨网络访问；将每个数据集扭曲为共同的参考；以及对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.