GENETIC ANALYSIS OF PLACE CELL STABILITY AND FUNCTION

描述(改编自申请人的摘要)： 建议的研究是理解外显记忆、对地点的记忆和 事件。记忆的形式由一种名为 海马体。有严重海马区损害的人通常表现为“逆行” 健忘症“，他们会失去对损害发生之前的事件的记忆 最严重的损失是最近发生的事件。这些人还 表现为“顺行性健忘症”，他们无法学习之后发生的事件 造成的损害。为了研究外显记忆，啮齿动物的空间记忆将被 用作模型。海马区受损的大鼠和小鼠通常无法 记住如何解决在损坏之前学到的空间问题，并且 在解决损坏后出现的新的空间问题方面存在障碍。这个 目标是了解分子、细胞和网络机制 这是空间记忆的基础。为此，海马区的“定位细胞”将 记录在转基因自由移动的小鼠身上。放置单元格表示 动物的位置，并被认为是神经图谱的基本单位 用于解决空间问题的环境。一个主要目标是 确定被称为长时程增强的突触可塑性机制 (LTP)参与Place细胞的形成和稳定。因此， LTP的不同分子机制将被遗传改变，并 将确定这些更改对放置单元属性的影响。 预计不同类型的Place单元格缺陷将由 不同种类的基因改变。此外，位置单元的知识 缺陷可以预测空间记忆缺陷的性质 在每个小鼠品系中。测试这些设备的计划的一个重要部分 行为学研究的预测是记录小鼠表现时的定位细胞 一项空间任务，让我们的预测得到检验。美国人民的一个希望 研究表明，理解LTP与外显记忆的耦合关系是通过 置入细胞将为药理设计提供坚实的基础 影响内存特定方面的代理。这已经成为一种常见的现象 生物学家的经验是，在分子水平上的理解允许 系统将以极高的精度控制。或许这个结局可以是 实现记忆，这是所有生物过程中最微妙的。

DESCRIPTION (Adapted from applicant's abstract): The overall goal of the proposed research is to understand explicit memory, memory for places and events. The form of memory is subserved by a brain structure called the hippocampus. People with severe hippocampal damage often show "retrograde amnesia", they lose memories about events before the damage occurred with the worst losses being for the most recent events. Such individuals also show "anterograd amnesia", they are unable to learn events that happen after the damage. To study explicit memory, spatial memory in rodents will be used as a model. Rats and mice with hippocampal damage are often unable to remember how to solve spatial problems learned before the damage, and are impaired in solving new spatial problems presented after the damage. The goal is to understand the molecular, cellular and network mechanisms that underlie spatial memory. To this end, hippocampal "place cells" will be recorded in genetically modified freely moving mice. Place cells signal the animal's location and are thought to be essential units of a neural map of the environment used in spatial problem solving. A major aim is to determine if the synaptic plasticity mechanism called long-term potentiation (LTP) participates in the formation and stabilization of place cells. Thus, different molecular mechanisms of LTP will be genetically altered and the effects of these alterations on place cell properties will be determined. It is expected that place cell defects of different kinds will be caused by genetic alterations of different kinds. Moreover, knowledge of place cell defects will allow predictions of the nature of the defect of spatial memory in each mouse strain. An important part of the plan to test these predictions with behavioral studies is to record place cells as mice perform a spatial task, allowing our predictions to be tested. One hope for the research is that understanding the coupling of LTP to explicit memory via place cells will provide a firm basis on which to design pharmacological agents that affect specific aspects of memory. It has been the common experience of biologists that understanding at the molecular level allows systems to be controlled with great precision. Perhaps this end can be achieved for memory, the most delicate of all biological processes.