The Dynamics of Memory Retrieval and Forgetting

记忆提取和遗忘的动力学

• 批准号: 7912373
• 负责人: Ehren L. Newman
• 金额: $ 5.05万
• 依托单位: BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-06-01 至 2013-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7912373
• 关键词: Address; Alzheimer' s Disease; Behavior; Cells; Clinical; Computer Simulation; Data; Data Analyses; Development; Disease; Environment; Generations; Hippocampus (Brain); Lighting; Maps; Medial; Memory; Methods; Modeling; Phase; Population; Post-Traumatic Stress Disorders; Protocols documentation; Rattus; Relative (related person); Research; Retrieval; Rewards; Series; Simulate; Stimulus; Testing; Theta Rhythm; Time; Work; addiction; base; entorhinal cortex; experience; forgetting; memory retrieval; public health relevance; research study; simulation

DESCRIPTION (provided by applicant): The specific aims of the research proposed here are to 1) test predictions, made by computational models, regarding the relationship between theta rhythms and memory retrieval and memory strength; and 2) further refine and develop these models. These models and their predictions, if verified, carry direct relevance for the development of clinical therapies for disorders such as Alzheimer's disease, addiction, and post-traumatic stress disorder (PTSD). Under Specific Aim #1, I will provide rats with extensive experience in two environments. Defining features of these environments will include the enclosure lighting and the behavior-reward contingency. I will record the activity of place cells in the hippocampus and grid cells in the medial entorhinal cortex as the rats perform pure-environment trials and mixed-environment trials. During pure-environment trials, the environmental features will remain fixed throughout the trial; I will use these trials to characterize the spatial tunings of all of the cells (i.e., the spatial map) in the two separate environments. During mixed-environment trials, the environmental features will be flipped between those that define the separate environments multiple times during each trial. I will infer, based on the population activity, which spatial map is activated at each moment during these mixed-environment trials. In Experiment 1, I will test whether the moment at which one spatial map turns off and the other takes its place occurs non-uniformly over the phases of ongoing theta rhythms. In Experiment 2, I will test whether it is possible to induce the partial retrieval of a spatial map and thereby shift the point at which the alternate spatial map activates as was predicted by my previously proposed model. In Experiment 3, I will test the correspondence between the rat's behavior and which spatial map is activated to test whether such manipulations could serve as a clinical therapy to alter behavior. In Experiment 4, I will explore the relative timing of hippocampal and entorhinal remapping. Under Specific Aim #2, I will use computational modeling to support the empirical work described under Specific Aim #1. Specifically, I will use the same models that generated the predictions that I will address under Specific Aim #1 to simulate the task that I will use to test these predictions. From these simulations, I will generate synthetic data on which I will verify the data analysis methods that I will use to infer which spatial map is active at each moment. These simulations will also allow me to develop the stimulus control protocol, for use during Experiment 2 of Specific Aim #1, that will most reliably generate partial retrieval. Most powerfully, they will allow me to generate additional testable predictions regarding the boundary conditions of the predictions described under Specific Aim #1 and thereby motivate my next series of experiments. PUBLIC HEALTH RELEVANCE: The research proposed here will explore how memories are retrieved, and why memories are forgotten. The results of this study will have direct relevance to the generation of clinical therapies for Alzheimer's disease, addiction, and post-traumatic stress disorder (PTSD).

描述（由申请人提供）：这里提出的研究的具体目的是1）计算模型对theta节奏与记忆检索和记忆强度之间关系的测试预测； 2）进一步完善并开发这些模型。这些模型及其预测（如果验证）具有直接相关性，以开发诸如阿尔茨海默氏病，成瘾和创伤后应激障碍（PTSD）等疾病的临床疗法。在特定的目标＃1下，我将在两个环境中为老鼠提供丰富的经验。这些环境的定义特征将包括外壳照明和行为回报的意外情况。当大鼠进行纯种环境试验和混合环境试验时，我将记录内侧内侧皮层中的位置细胞的活性。在纯环境试验中，环境特征将在整个试验过程中保持固定。我将使用这些试验来表征两个单独环境中所有单元格（即空间图）的空间调谐。在混合环境试验中，环境特征将在每个试验中多次定义单独环境的人之间进行翻转。我将根据人口活动来推断，在这些混合环境试验期间的每一刻，空间图被激活。在实验1中，我将测试一个空间图关闭和另一个空间图的时刻是否在持续的theta节奏的阶段不均匀地发生。在实验2中，我将测试是否有可能诱导空间图的部分检索，从而改变替代空间图激活的点，如我先前提出的模型所预测的那样。在实验3中，我将测试大鼠行为和激活哪个空间图之间的对应关系，以测试此类操作是否可以作为改变行为的临床疗法。在实验4中，我将探讨海马和内嗅重映射的相对时机。在特定的目标＃2下，我将使用计算建模来支持特定目标＃1中描述的经验工作。具体来说，我将使用相同的模型生成的预测，这些预测将在特定目标＃1下解决，以模拟我将用来测试这些预测的任务。从这些模拟中，我将生成合成数据，在这些数据上，我将验证我将用来推断哪个空间映射在每时每刻处于活动状态的数据分析方法。这些模拟还将使我能够制定刺激控制方案，以供特定目标1的实验2期间使用，这将最可靠地产生部分检索。最有力的是，它们将使我能够就特定目标1中描述的预测的边界条件产生其他可测试预测，从而激发我的下一系列实验。 公共卫生相关性：这里提出的研究将探讨如何检索记忆以及为什么被遗忘的记忆。这项研究的结果将与阿尔茨海默氏病，成瘾和创伤后应激障碍（PTSD）的临床疗法的产生直接相关。