A novel paradigm to investigate memory reconsolidation in adult and aged rats

研究成年和老年大鼠记忆重建的新范例

• 批准号: 7910430
• 负责人: BETHANY J. JONES
• 金额: $ 5.48万
• 依托单位: UNIVERSITY OF ARIZONA
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-15 至 2012-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7910430
• 关键词: Accounting; Address; Adult; Age; Aging; Animal Behavior; Animal Model; Animals; Area; Behavioral; Cells; Cognition Disorders; Data; Dementia; Environment; Episodic memory; Event; Goals; Hippocampus (Brain); Human; Impairment; Investigation; Knowledge; Learning; Light; Location; Measures; Memory; Memory Disorders; Memory impairment; Molecular; Names; Nature; Outcomes Research; Pattern; Phase; Post-Traumatic Stress Disorders; Prevention; Process; Public Health; Rattus; Research; Rest; Rewards; Rodent; Running; Sleep; Testing; Time; Training; Update; Visit; Water; Work; age related; aged; experience; extracellular; innovation; insight; memory process; memory recall; neuromechanism; novel; public health relevance; relating to nervous system; research study; sugar

DESCRIPTION (provided by applicant): Reconsolidation is the process by which memories which have become unstable due to re-instantiation (remembering) are re-stabilized. During this process, new information can become incorporated into old memories. Because reconsolidation is a fundamental phase of memory processing, deficits in reconsolidation could partially account for impairments in episodic memory associated with aging and various memory disorders. The long-term goals of the proposed research are to determine the network mechanisms by which memory reconsolidation occurs and to assess if and how these mechanisms change with aging. The objectives of this proposed study are to study reconsolidation of positively motivated spatial memory in both young and aged rats and to investigate the neural substrate associated with reconsolidation. In order to fulfill these objectives, three specific aims will be addressed. (1) The first aim is to investigate the effect of experimental context on reconsolidation of positively motivated spatial memories. To pursue this aim, adult rats will be trained on Day 1 to run to 3 different feeders (List 1) for sugar water reward. On Day 2, rats will be trained to run to 3 different feeders (List 2) in either the same or a different experimental context than that used on Day 1. On Day 3, rats must recall List 1, and reconsolidation will be measured as the percent of incorrect visits made to List 2 feeders. (2) The second aim is to measure the extent to which post- task replay of neural activity reflecting List 1 and List 2 memory items correlates with the errors made by the animals during memory recall. To pursue this aim, extracellular activity in area CA3 of the hippocampus will be recorded in adult rats as they perform a condensed version of the behavioral task described above. (3) The third aim is to measure memory reconsolidation in aged animals. To pursue this aim, the behavioral experiment described above will be conducted with aged rats. This research will provide a new animal model for memory reconsolidation, insights into its neural mechanisms, and the first data illustrating how this process may change with age, thus shedding light on the dynamic nature of memory and age-related memory impairment. PUBLIC HEALTH RELEVANCE: Relevance to public health: Memory impairments are associated with aging and characterize various cognitive disorders, such as dementia and post-traumatic stress disorder. Studying the process by which memories are maintained and updated after recollection and how this process changes with age will contribute to a better understanding and, ultimately, prevention and treatment of such memory deficits.

描述（由申请人提供）：重新巩固是使由于重新实例化（记忆）而变得不稳定的记忆重新稳定的过程。在此过程中，新信息可以融入旧记忆中。由于再巩固是记忆处理的基本阶段，因此再巩固的缺陷可能部分解释与衰老和各种记忆障碍相关的情景记忆损伤。拟议研究的长期目标是确定记忆重新巩固发生的网络机制，并评估这些机制是否以及如何随着衰老而变化。这项研究的目的是研究年轻和老年大鼠积极动机空间记忆的再巩固，并研究与再巩固相关的神经基质。为了实现这些目标，将实现三个具体目标。 （1）第一个目标是研究实验环境对积极动机空间记忆重新巩固的影响。为了实现这一目标，成年大鼠将在第一天接受训练，跑向 3 个不同的喂食器（列表 1）以获得糖水奖励。第 2 天，将训练大鼠在与第 1 天相同或不同的实验环境中跑向 3 个不同的喂食器（列表 2）。第 3 天，大鼠必须回忆起列表 1，并且将重新巩固测量为对列表 2 供料器进行错误访问的百分比。 (2) 第二个目的是测量反映列表 1 和列表 2 记忆项目的神经活动的任务后重放与动物在记忆回忆过程中所犯错误的相关程度。为了实现这一目标，当成年大鼠执行上述行为任务的浓缩版本时，将记录海马 CA3 区的细胞外活动。 (3) 第三个目标是测量老年动物的记忆再巩固情况。为了实现这一目标，将用老年大鼠进行上述行为实验。这项研究将为记忆再巩固提供一种新的动物模型，深入了解其神经机制，并提供第一个数据来说明这一过程如何随年龄而变化，从而揭示记忆的动态性质和与年龄相关的记忆障碍。 公共卫生相关性： 与公共健康的相关性：记忆障碍与衰老有关，是各种认知障碍的特征，例如痴呆和创伤后应激障碍。研究记忆在回忆后维持和更新的过程，以及这个过程如何随着年龄的变化而变化，将有助于更好地理解并最终预防和治疗此类记忆缺陷。