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）：重新整合是由于重新建立（记住）而变得不稳定的记忆被重新稳定的过程。在此过程中，新信息可以纳入旧记忆中。由于重新溶解是记忆处理的基本阶段，因此重新溶解的缺陷可以部分解释与衰老和各种记忆障碍相关的情节记忆的损害。拟议研究的长期目标是确定发生记忆重新稳固的网络机制，并评估这些机制是否随着衰老而变化。这项拟议的研究的目的是研究年轻大鼠和老年大鼠积极动机的空间记忆的重新整合，并研究与重新溶解有关的神经底物。为了实现这些目标，将解决三个具体目标。 （1）第一个目的是研究实验环境对重新整合空间记忆的重新整合的影响。为了实现这一目标，成年大鼠将在第1天接受培训，以跑到3种不同的喂食器（清单1）以获得糖水奖励。在第2天，将训练大鼠在与第1天相同或不同的实验环境中跑到3个不同的进料器（列表2）。在第3天，大鼠必须召回清单1，并且将重新溶解为列出列表的百分比，以列出列出2个喂食器的错误访问百分比。 （2）第二个目的是测量反映清单1和列表的神经活动后任务重播的程度2与记忆项相关，与动物记忆回忆中动物的错误相关。为了实现这一目标，在成年大鼠执行上述行为任务的凝结版本时，将记录海马的CA3区域CA3区域的细胞外活动。 （3）第三个目的是测量老年动物的记忆重新整合。为了追求这一目标，上述的行为实验将与老年大鼠进行。这项研究将为记忆重新整合，对其神经机制的见解提供新的动物模型，以及第一个数据，说明了该过程如何随着年龄的变化而变化，从而阐明了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： 与公共卫生的相关性：记忆障碍与衰老有关，并表征各种认知障碍，例如痴呆症和创伤后应激障碍。研究回忆后维持和更新记忆的过程以及该过程如何随着年龄的变化而变化将有助于更好地理解，最终，预防和治疗此类记忆缺陷。