Genetic-assisted, full brain scale integrated activity mapping with MRI

项目总结 为了理解认知、行为和病理的细胞基础，有必要绘制不同的 在不同的生物过程中参与的大脑区域和回路 同样的动物。我建议通过建立一种新的遗传方法来实现这一目标，以全面记录大脑 活着的哺乳动物的综合细胞活动。我的研究提案的目的是应用一种新的基因 表达遗传编码磁性指示物的细胞系综(GATE)的活性诱导标记 (GEMIS)，通过磁共振成像(MRI)进行全面的大脑综合活动图。我们会放映 不同GEMI及其组合用于高信噪比的高分辨率脑活动地形图 首先在脑片中，然后在体内，使用病毒和转基因小鼠。成功实施 这种方法将对系统神经科学产生变革性的影响，因为它将允许绘制 在相同的动物中，激活了学习和记忆巩固和提取过程中的大脑回路。 重要的是，所提出的方法将有助于揭示不同精神病患者和 神经疾病，还跟踪治疗干预后脑图的变化，同样是在相同的 动物。 我们将实现两个具体目标： 特定目标1--确定综合活动的最佳vGATE-GEMI(S)的组合筛选 磁共振成像在培养的大鼠脑片中的定位。 带有vGATE-GEMI的病毒载体及表达分析。 1B-化学诱导的vGATE-GEMI辅助MRI整合活性定位。 2C-将GEMI表达和标记细胞数与MRI信号检测相关联。 特定目的2-通过核磁共振vGATE辅助的整合活动图在体内验证GEMI。 2a-化学诱导和感官体验诱发的MRI活动图。 2B转基因小鼠进行完整的全脑活动核磁共振成像。 2C-相关的GEMI表达和标记的细胞数用于MRI信号检测。

PROJECT SUMMARY To understand the cellular basis of cognition, behavior and pathology, it is necessary to map the different participating brain regions and circuits that participate during the different biological processes and do so I the same animals. I propose to reach this goal by establishing a novel genetic method for full brain scale recording of integrated cellular activity in living mammals. The aim of my research proposal is to apply a novel Genetic Activity-induced Tagging of cell Ensembles (GATE) to express Genetically Encoded Magnetic Indicators (GEMIs) for full brain scale integrated activity mapping by magnetic resonance Imaging (MRI). We will screen different GEMIs and their combinations for high-resolution mapping of brain activity with high signal-to-noise ratio, first in brain slices and then in vivo, both using viruses and transgenic mice. The successful implementation of this method would make a transformational impact on systems neuroscience as it would allow mapping of activated brain circuits in learning and memory consolidation and retrieval processes in the same animals. Importantly, the proposed method would help to reveal the brain activity maps in the different psychiatric and neurological disease and also track changes in brain maps after therapeutic interventions, again in the same animals. We will perform 2 Specific Aims: Specific Aim 1– A combinatorial screen to identify an optimal vGATE-GEMI(s) for integrated activity mapping by MRI in cultured rat brain slices. 1A– Viral vectors with vGATE-GEMIs and expression analyses. 1B– Chemically-induced vGATE-GEMI assisted integrated activity mapping by MRI. 2C– Correlate GEMI expression and number of labeled cells to MRI signal detection. Specific Aim 2– In vivo validation of GEMI by vGATE-assisted integrated activity mapping by MRI. 2A– Chemically-induced and sensory experience evoked MRI activity maps. 2B– Transgenic mice for integrated full brain scale activity mapping by MRI. 2C– Correlate GEMI expression and number of labelled cells for MRI signal detection.