Memory and Hippocampus: Anaylsis of Retrograde Amnesia

罗伯特·E·克拉克博士NSF提案编号：0237053NSF提案标题：记忆与海马体：逆行性失忆症的分析大量的工作一直致力于了解一种称为海马体的大脑结构如何有助于记忆功能。对这一工作传统特别重要的一个现象是时间分级逆行性健忘症(TGRA)。TGRA指的是发现在记忆受损之前很久学习的信息(记忆)通常比最近学习的信息更容易获得。例如，海马体受损的人，对在大脑受损之前学习到的事实和事件几乎没有记忆，但保留了在损伤之前就已经学会的记忆。因此，最初依赖于海马体的记忆逐渐变得不依赖于海马体。一个关键的问题是海马体的活动是如何参与这一过程的。这些实验提供了一个系统的研究，即海马体必须在何时以及在多长时间内活跃才能支持记忆。在大鼠身上，可逆性损伤将被用来选择性地灭活海马体(通过注入一种在不损害神经元的情况下扰乱海马体功能的药物)。因此，在学习和记忆过程的不同阶段，海马体可以被打开或关闭。也就是说，可逆性损伤将在记忆的学习、保持或恢复阶段的不同阶段应用，以确定海马体活动是否以及何时对记忆重要。这些可逆的损害是通过植入渗透性微泵(可以连续许多天缓慢地将药物输送到海马体的装置)造成并持续很长一段时间的。这些结果将为学习后的海马体活动如何有助于建立长期记忆提供重要的见解。弄清这种记忆丧失的模式(TGRA)对于了解记忆是如何在大脑中组织和存储至关重要的。拟议的活动将为研究生和博士后提供心理学、认知科学和神经科学方面的研究培训。

Robert E. Clark, Ph.D.NSF Proposal Number: 0237053NSF Proposal Title: Memory and Hippocampus: Analysis of Retrograde AmnesiaA considerable body of work has been directed toward understanding how a brain structure known as the hippocampus contributes to memory function. A phenomenon that has been especially important to this tradition of work is temporally-graded retrograde amnesia (TGRA). TGRA refers to the finding that information (memories) learned long before the onset of memory impairment are often spared relative to information learned more recently. For example, humans who have sustained damage to the hippocampus, have little or no memory for facts and events that was learned just prior to their brain damage, but retain memories that were learned well before the damage. Accordingly, memory that is initially hippocampus-dependent, gradually becomes hippocampus-independent. A critical question is how hippocampal activity participates in this process.These experiments provide a systematic investigation of when and for how long the hippocampus must be active to support memory. Using rats, reversible lesions will be used to selectively inactivate the hippocampus (by infusing a drug that disrupts hippocampal function without damaging the neurons). Accordingly, the hippocampus can be turned on or off during different phases of the learning and memory process. That is, reversible lesions will be applied during different portions of the learning, retention, or retrieval phase of memory to determine if and when hippocampal activity is important for memory. These reversible lesions are created and sustained for long periods of time with implanted osmotic minipumps (devices that can slowly deliver the drugs to the hippocampus continuously for many days). These results will provide important insights into how hippocampal activity following learning contributes to the establishment of long-term memory. Clarifying this pattern of memory loss (TGRA) is critical for understanding how memory is organized and stored in the brain. The proposed activities will provide research training for graduate students and post-doctoral students in psychology, cognitive science, and neuroscience.