Genetics of spatial learning and memory

空间学习和记忆的遗传学

• 批准号: 6921974
• 负责人: VALERIE J BOLIVAR
• 金额: $ 17.31万
• 依托单位: WADSWORTH CENTER
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-07-15 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6921974
• 关键词: animal genetic material tag; behavior test; behavioral /social science research tag; behavioral genetics; cognition disorders; exploratory behavior; gene expression; genetic regulation; laboratory mouse; learning disorders; memory disorders; open field behavior; quantitative trait loci; space perception

DESCRIPTION (provided by applicant): Elucidation of the genetics involved in cognitive dysfunction is important for potential therapeutic and educational intervention. Over the past decade, much attention has focused on the role of genetics in specific types of cognitive dysfunction in children and the elderly. In some cases specific genes have been implicated (e.g., Alzheimer's disease). However, cognition is complex and there are many genes that influence it. Our long-term goal is to find genes involved in learning inefficiencies, so that treatments can be devised to help those with cognitive impairments. The objective of this application is to examine the role of genetics in spatial learning. Spatial learning provides us with a representation of objects in the world around us and is critical for everyday cognition. Three measures of spatial learning in rodents, the Barnes Maze (BM), the Morris water maze (MWM) and the Spatial/ Object Novelty in the Open Field Assay (SON) will be used in this research project. We propose to investigate the role of genetics in all three assays, by evaluating multiple measures of performance. The specific aims of this application are: 1). Evaluate potential order effect when testing the same mice in i) both the BM and MWM and ii) both spatial and cued versions of the MWM, 2). Determine genetic loci involved in spatial learning and memory as measured by our behavioral test battery, and 3). Confirm and/or narrow down genetic loci with knockout/ congenic strains. We will eventually use genomic techniques to identify candidate genes, however, this is beyond the scope of the present grant proposal. As this is our first venture into the genetic dissection of spatial learning and memory, this project is exploratory in nature and therefore is being submitted as an Exploratory/Developmental Research (R21) grant. Our preliminary data provides evidence that multiple measures will yield a plethora of information on inbred strain performance differences in spatial learning and memory. More detailed analyses of the paths used by the mice to navigate the BM MWM should provide even more in-depth information. This new, exciting line of investigation should have high impact on the field, by providing baseline data of spatial learning and memory performance for commonly used in strains as well as providing genetic loci for future investagion.

描述（由申请人提供）：阐明认知功能障碍涉及的遗传学对于潜在的治疗和教育干预非常重要。在过去的十年中，人们的注意力集中在遗传学在儿童和老年人特定类型的认知功能障碍中的作用。在某些情况下，涉及特定基因（例如， 阿尔茨海默病）。然而，认知是复杂的，影响它的基因有很多。 我们的长期目标是找到与学习效率低下有关的基因，以便设计出治疗方法来帮助那些患有认知障碍的人。此应用程序的目的是检查遗传学在空间学习中的作用。空间学习为我们提供了周围世界物体的表征，对于日常认知至关重要。啮齿类动物空间学习的三种测量方法：巴恩斯迷宫 (BM)、莫里斯水迷宫 (MWM) 和空间/物体 本研究项目将使用新颖的开放场测定（SON）。我们建议通过评估多种性能指标来研究遗传学在所有三种测定中的作用。该应用程序的具体目标是：1）。评估在 i) BM 和 MWM 以及 ii) MWM 的空间版本和提示版本中测试相同小鼠时的潜在顺序效应，2)。确定通过我们的行为测试电池测量的空间学习和记忆涉及的遗传位点，以及 3)。通过敲除/同源菌株确认和/或缩小遗传位点范围。我们最终将使用基因组技术来识别候选基因，但是，这超出了当前拨款提案的范围。由于这是我们第一次尝试空间学习和记忆的基因解剖，因此该项目本质上是探索性的，因此正在作为探索性/发展研究 (R21) 拨款提交。我们的初步数据提供的证据表明，多种措施将产生大量关于近交系在空间学习和记忆方面的表现差异的信息。对小鼠用于导航 BM MWM 的路径进行更详细的分析应该提供更深入的信息。通过提供菌株常用的空间学习和记忆性能的基线数据以及为未来的研究提供遗传位点，这一新的、令人兴奋的研究路线应该对该领域产生重大影响。