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

描述(申请人提供)：重新巩固是由于重新实例化(记忆)而变得不稳定的记忆被重新稳定的过程。在这个过程中，新的信息可以被合并到旧的记忆中。因为重新巩固是记忆处理的一个基本阶段，重新巩固的缺陷可以部分解释与衰老和各种记忆障碍相关的间歇性记忆损害。这项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年龄的增长而变化。本研究的目的是研究青年和老年大鼠正向动机空间记忆的再巩固，并探讨与再巩固相关的神经底物。为了实现这些目标，将实现三个具体目标。(1)本研究的第一个目的是考察实验情境对正向动机空间记忆再巩固的影响。为了实现这一目标，成年大鼠将在第一天接受训练，跑到三个不同的喂食器(列表1)前，以获得糖水奖励。在第二天，大鼠将被训练跑到三个不同的喂食器(列表2)，在与第一天相同或不同的实验环境中。在第三天，大鼠必须回忆列表1，再巩固将被测量为错误访问列表2喂食器的百分比。(2)第二个目标是测量反映列表1和列表2的记忆项目的任务后重放与动物在记忆回忆过程中犯的错误相关的程度。为了实现这一目标，成年大鼠在执行上述行为任务的浓缩版本时，将记录其海马区CA3区的细胞外活动。(3)第三个目的是测量老年动物的记忆再巩固。为了达到这一目的，上述行为实验将在老龄大鼠身上进行。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，并首次提供说明这一过程如何随年龄变化的数据，从而揭示记忆的动态性质和与年龄相关的记忆损害。 公共卫生相关性： 与公共健康相关：记忆障碍与衰老有关，并表现为各种认知障碍，如痴呆症和创伤后应激障碍。研究记忆在回忆后维持和更新的过程以及这一过程如何随年龄变化将有助于更好地理解并最终预防和治疗这种记忆缺陷。

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.