Tools for Dissecting Proximal and Distal CA1 Contributions to Learning and Memory

项目摘要 人类和动物的数据表明，海马体编码的事件和空间的背景下，他们 发生.为了理解这是如何实现的，我们将使用一种系统级的方法， 对比了老鼠海马体内专门微电路的功能。重点抓好 CA1的近端和远端段，被认为编码动物的空间位置和位置 环境中的物体。为了控制这些区域在行为过程中的活动，我们将开发新的 可以用于在CA1的特定片段中表达抑制性视蛋白ArchT的遗传工具。针对性 然后，在新开发的位置和物体学习过程中，激光刺激将用于使这些部分沉默 任务我们预测，视觉空间学习将需要近端CA1的活动，而物体学习将需要近端CA1的活动。 需要远端CA1的活性。从这些分析中获得的信息将改进我们的模型， 海马组织，让我们更好地了解这个结构如何存储和检索不同的 记忆的类型。此外，这些工具可用于人类疾病的小鼠模型中，以改变活性或功能。 控制海马体不同部分的基因表达。

Project Summary Human and animal data indicate that the hippocampus encodes events and the spatial context in which they occur. To understand how this is accomplished, we will use a systems-level approach that compares and contrasts the function of specialized microcircuits within the mouse hippocampus. We will focus on the proximal and distal segments of CA1, which are thought to encode an animal’s spatial location and the location of objects in the environment. To control the activity of these regions during behavior, we will develop new genetic tools that can be used to express the inhibitory opsin ArchT in specified segments of CA1. Targeted laser stimulation will then be used to silence these segments during newly developed place and object learning tasks. We predict that visuospatial learning will require activity in proximal CA1 while object learning will require activity in distal CA1. The information gained from these analyses will improve our models of hippocampal organization and allow us to better understand how this structure stores and retrieves distinct types of memory. In addition, these tools can be used in mouse models of human disease to modify activity or control gene expression in distinct segments of the hippocampus.