The role of the hippocampus in protecting recently formed memories from interfering sensory stimulation during memory consolidation

海马体在记忆巩固过程中保护最近形成的记忆免受感觉刺激干扰的作用

• 批准号: RGPIN-2020-04795
• 负责人: Hardt, Oliver
• 金额: $ 2.4万
• 依托单位: McGill University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=764036
• 关键词: role; hippocampus; protecting; recently; formed

Damage to brain areas of the medial-temporal lobe, such as the hippocampus, causes a pronounced memory deficit in humans and non-human animals, impairing the laying down of long-lasting memories for facts and events (declarative memories). These phenomena establish that the hippocampus plays a fundamental role in memory. Yet, despite decades of research, it remains unresolved in what way this brain system promotes forming long-term declarative memories, and various theoretical models have been developed and controversially discussed without reaching a commonly accepted resolution. My research program aims to address this issue. As part of our progress towards understanding the role of hippocampus in memory formation, we have recently proposed a novel theoretical framework, in which we argue that damage to the hippocampus impairs the normal brain system mechanisms that prevent the stream of ongoing experiences from rapidly eroding the records of its own past. Support for this original perspective comes from studies in amnesic patients as well as healthy humans in which the amount of stimulation after learning was carefully controlled: Participants were first presented with a prose description of an event. Immediately afterwards, the lights in the experimental room were lowered and participants simply stayed in the room relaxing for one hour, but not sleeping. Then they were asked to recall the story. When the lights stayed on, amnesic patients were not able to recall any part of the story. However, when the room lights were dimmed, their ability to remember significantly improved. Healthy participants also benefited from staying in the dark after learning. HQP in my lab has developed a corresponding rat paradigm and replicated these basic results using a novel object recognition task. Based on our recent progress, the present project thus will pursue the following objectives: (1) What type of sensory stimulation can impair the forming of object recognition memories in rats? How soon after learning and for how long need new memories be protected from sensory stimulation? (2) What neurobiological processes in the hippocampus promote the long-term retention of new memories? The outcomes of this project will advance my long-term goal to understand how the hippocampus contributes to memory, addressing a question of broad interest to basic and clinical scientist and the general public.

大脑中颞叶区域的损伤，如海马体，会导致人类和非人类动物明显的记忆缺陷，损害对事实和事件的持久记忆（陈述性记忆）的建立。这些现象表明海马体在记忆中起着重要作用。然而，尽管经过了几十年的研究，这个大脑系统是如何促进长期陈述性记忆形成的，仍然没有得到解决，各种理论模型已经发展起来，并有争议地讨论，但没有达成一个普遍接受的解决方案。我的研究计划旨在解决这个问题。作为我们理解海马体在记忆形成中的作用的一部分，我们最近提出了一个新的理论框架，在这个框架中，我们认为海马体的损伤会损害正常的大脑系统机制，从而阻止正在进行的经历流迅速侵蚀其过去的记录。对失忆症患者和健康人的研究支持了这一原始观点，在这些研究中，学习后的刺激量被仔细控制：参与者首先看到一件事的散文描述。紧接着，实验室内的灯光被调暗，参与者只是在房间里放松一个小时，但不睡觉。然后他们被要求回忆这个故事。当灯亮着时，失忆症患者无法回忆起故事的任何部分。然而，当房间灯光变暗时，他们的记忆能力显著提高。健康的参与者也从学习后的黑暗中受益。我实验室的HQP开发了一个相应的老鼠范例，并使用一个新的物体识别任务复制了这些基本结果。基于我们最近的进展，本项目将追求以下目标：(1)什么类型的感官刺激会损害大鼠物体识别记忆的形成？学习后的新记忆需要多长时间才能不受感官刺激的保护？(2)海马体中的哪些神经生物学过程促进了新记忆的长期保留？这个项目的结果将推进我的长期目标，了解海马体如何促进记忆，解决基础和临床科学家以及公众广泛感兴趣的问题。