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

用于剖析近端和远端 CA1 对学习和记忆贡献的工具

基本信息

批准号：
9455391
负责人：
Brian J Wiltgen
金额：
$ 18.52万
依托单位：
UNIVERSITY OF CALIFORNIA AT DAVIS
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-09-25 至 2019-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9455391
关键词：
Adenoviruses Affect Alzheimer&apos s Disease Anatomy Animals Anxiety Area Basic Science Behavior Behavioral Cells Clinical Communication Data Disease model Distal Dorsal Environment Epilepsy Event Exhibits Fragile X Syndrome Gene Expression Genetic Goals Hippocampus (Brain)Human Infusion procedures Lasers Lateral Lead Learning Location LoxP-flanked allele Medial Memory Memory Disorders Memory impairment Mental Depression Mental Health Methods Modeling Mus Neurobiology Neurofibromatoses Neurons Opsin Output Pathology Pathway interactions Pharmaceutical Preparations Pharmacology Prevention Research Personnel Rett Syndrome Series Signal Pathway Specific qualifier value Stroke Structure System Testing Time Tissues Transgenic Mice Transgenic Organisms Traumatic Brain Injury Tuberous Sclerosis Viral Visuospatial animal data base communication behavior conditioned fear design entorhinal cortex experimental study hippocampal pyramidal neuron human data human disease improved insight memory consolidation memory encoding mouse model nervous system disorder novel object recognition optogenetics pre-clinical prevent promoter selective expression tool way finding

项目摘要

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.

项目摘要人类和动物的数据表明，海马体编码事件以及它们所处的空间环境发生。为了理解这是如何实现的，我们将使用系统级方法来比较和对比了小鼠海马区内专门的微电路的功能。我们将重点关注 CA1的近端和远端片段，被认为编码了动物的空间位置和位置环境中的对象。为了在行为过程中控制这些区域的活动，我们将开发新的可用于在CA1的特定片段中表达抑制性视蛋白ARCHT的基因工具。目标明确然后，在新开发的位置和物体学习期间，将使用激光刺激来使这些片段静音任务。我们预测，视觉空间学习将需要CA1近端的活动，而物体学习将需要需要在CA1远端活动。从这些分析中获得的信息将改进我们的模型并使我们能够更好地理解该结构是如何存储和提取不同的内存类型。此外，这些工具可以用于人类疾病的小鼠模型，以修改活动或控制海马体不同部分的基因表达。