GENETIC ANALYSIS OF PLACE CELL STABILITY AND FUNCTION

描述（改编自申请人摘要）： 一项提议的研究是了解外显记忆，地点记忆， 事件 记忆的形式是由一种叫做 海马体。 海马损伤严重的人通常表现出“逆行”， 健忘症”，他们失去了关于损害发生前的事件的记忆， 损失最大的是最近发生的事件。 这些人也 表现出“顺行性遗忘症”，他们无法学习之后发生的事件 造成的伤害 为了研究外显记忆，啮齿动物的空间记忆将被 用作模型。 海马损伤的大鼠和小鼠通常无法 记住如何解决空间问题之前学习的损害， 在解决损坏后出现的新空间问题方面受损。 的 目标是了解分子，细胞和网络机制， 是空间记忆的基础 为此，海马“定位细胞”将被 在转基因自由活动小鼠中记录的。 放置单元格表示 动物的位置，被认为是神经地图的基本单位， 解决空间问题的环境。 一个主要目标是 确定突触可塑性机制，称为长时程增强， (LTP)参与定位细胞的形成和稳定。 因此，在本发明中， LTP的不同分子机制将被遗传改变， 将确定这些改变对位置细胞特性的影响。 预期不同种类的位置单元缺陷将由以下引起： 不同种类的基因改变。 此外，位置细胞的知识 缺陷将允许预测空间记忆缺陷的性质 在每种小鼠品系中。 计划的一个重要部分是测试这些 行为研究的预测是记录小鼠的位置细胞， 一个空间任务，让我们的预测得到检验。 一个希望， 研究表明，理解LTP与外显记忆的耦合， 定位细胞将提供一个坚实的基础上，设计药理学 影响记忆特定方面的代理人。 这是常见的 生物学家的经验是，在分子水平上的理解可以 系统需要精确控制。 也许这一结局可以 记忆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.