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

项目摘要 为了理解认知、行为和病理的细胞基础，有必要绘制不同的细胞图。 参与不同生物过程的大脑区域和回路， 同样的动物。我建议通过建立一种新的全脑尺度记录的遗传方法来达到这一目标 完整的细胞活动。我的研究计划的目的是应用一种新的遗传学 活性诱导的细胞系综标记（GATE）以表达遗传编码的磁性指示剂 （GEMI）用于通过磁共振成像（MRI）进行全脑尺度整合活动映射。我们将筛选 不同的GEMI及其组合，用于高信噪比的大脑活动的高分辨率映射 首先在脑切片中，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 在同一动物的学习和记忆巩固和检索过程中激活大脑回路。 重要的是，所提出的方法将有助于揭示不同精神病患者的大脑活动图， 神经系统疾病，并在治疗干预后跟踪脑地图的变化，同样在同一 动物 我们将实现两个具体目标： 具体目标1-鉴定整合活性的最佳vGATE-GEMI的组合筛选 在培养的大鼠脑切片中通过MRI映射。 1A-具有vGATE-GEMI的病毒载体和表达分析。 1B-通过MRI的化学诱导的vGATE-GEMI辅助的整合活性映射。 2C-将GEMI表达和标记细胞的数量与MRI信号检测相关联。 具体目标2-通过MRI进行的vGATE辅助整合活性标测对GEMI进行体内验证。 2A-化学诱导和感觉体验诱发的MRI活动图。 2B-通过MRI进行整合的全脑尺度活动映射的转基因小鼠。 2C-将GEMI表达与标记细胞的数量相关联以用于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.