Imaging Neuronal Activity One Population at a Time

描述(由申请人提供)：我们在神经科学中面临的最困难的问题之一是理解神经网络如何处理信息。了解网络如何运行取决于了解它的组成单元类做什么--即它们的活动模式是什么，以及它们与其他单元类的活动模式是如何关联的。在这里，我们提出了一种新的方法来监测神经系统的活动。这种方法结合了遗传和光学成像技术。遗传学允许以特定的细胞类别为目标，光学成像允许以高空间和时间分辨率监测每一类别细胞的活动。该方法是围绕一种标记蛋白质建立的，具体目标如下：目标1和目标2侧重于构建与蛋白质反应产生活性指示剂的化合物，目标3侧重于测试指示剂的性能(测量其选择性、动态范围和动力学)。该工具具有广泛的应用，包括基础和应用，从监测发育和成熟神经系统中的细胞间通讯到监测神经活性药物的作用(有效性和选择性)。

DESCRIPTION (provided by applicant): One (1) of the most difficult problems we face in neuroscience is understanding how neuronal networks process information. Understanding how a network operates depends on knowing what its component cell classes do-that is what their activity patterns are and how they relate to the activity patterns of other cell classes. Here we propose a new method for monitoring activity in neuronal systems. The method combines genetic and optical imaging techniques. Genetics allows specific cell classes to be targeted, and optical imaging allows the activity of the cells in each class to be monitored with high spatial and temporal resolution. The method is built around a marker protein, and the specific aims are as follows: Aims 1 and 2 focus on building compounds that react with the protein to produce activity-indicators, and Aim 3 focuses on testing the performance of the indicators (measuring their selectivity, dynamic range and kinetics). This tool has broad applications, both basic and applied, from monitoring cell-to-cell communication in the developing and mature nervous system to monitoring the actions (effectiveness and selectivity) of neuroactive drugs.