Genetics of spatial learning and memory

描述(由申请人提供)：阐明与认知功能障碍有关的遗传学对于潜在的治疗和教育干预很重要。在过去的十年里，人们非常关注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，特定基因已被牵连(例如， 阿尔茨海默病)。然而，认知是复杂的，影响它的基因很多。 我们的长期目标是找到与学习效率低下有关的基因，这样就可以设计出治疗方法来帮助那些认知障碍的人。这个应用程序的目的是研究遗传学在空间学习中的作用。空间学习为我们提供了对周围世界物体的表征，对日常认知至关重要。啮齿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 本研究项目将使用开放领域测试(SON)中的新颖性。我们建议通过评估多项性能指标来研究遗传学在所有三种检测中的作用。本申请的具体目的是：1)。当测试相同的小鼠时，评估潜在的顺序效应：i)BM和MWM，以及ii)MWM的空间和线索版本，2)。通过我们的行为测试组合来确定与空间学习和记忆有关的遗传基因座，以及3)。用基因敲除/同源菌株确认和/或缩小遗传位点。我们最终将使用基因组技术来识别候选基因，然而，这超出了目前拨款提案的范围。由于这是我们对空间学习和记忆的基因解剖的第一次冒险，这个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了证据，证明多项措施将产生大量关于近亲交配品系在空间学习和记忆方面的表现差异的信息。对老鼠导航BM MWM的路径进行更详细的分析应该会提供更深入的信息。这一新的、令人兴奋的研究路线应该会对这一领域产生很大的影响，因为它将为常用菌株提供空间学习和记忆表现的基线数据，并为未来的研究提供遗传位点。

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.