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: 2020
• 资助国家: 加拿大
• 起止时间: 2020-01-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=717212
• 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.

大脑内侧颞叶区域的损伤，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长期记忆(陈述性记忆)。这些现象证实了海马体在记忆中起着基本的作用。然而，尽管经过了几十年的研究，这个大脑系统是如何促进形成长期陈述性记忆的仍然没有解决，各种理论模型已经被开发出来，并引起了争议，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。作为我们在理解海马体在记忆形成中的作用的进展的一部分，我们最近提出了一个新的理论框架，在该框架中，我们认为海马体的损伤会损害正常的大脑系统机制，该机制防止正在进行的经验流迅速侵蚀其自身过去的记录。对这一原始观点的支持来自对健忘症患者和健康人的研究，在这些研究中，学习后的刺激量得到了仔细的控制：参与者首先被展示了对一个事件的散文描述。随后，实验室的灯光立即被调低，参与者只是在房间里放松了一个小时，但没有睡觉。然后，他们被要求回忆这个故事。当灯继续亮着时，健忘症患者无法回忆起故事的任何部分。然而，当房间的灯光变暗时，他们的记忆能力显著提高。健康的参与者也受益于学习后呆在黑暗中。HQP在我的实验室里开发了一个相应的老鼠范例，并使用一种新颖的物体识别任务复制了这些基本结果。基于我们的最新进展，本项目将追求以下目标：(1)什么类型的感觉刺激可以损害大鼠物体识别记忆的形成？学习后多久，新记忆需要多长时间不受感觉刺激的影响？(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持？ 这个项目的结果将推进我的长期目标，了解海马体如何有助于记忆，解决一个基础和临床科学家以及普通公众广泛感兴趣的问题。