Using a specialized behavior to study the neural mechanisms of episodic memory

使用专门的行为来研究情景记忆的神经机制

• 批准号: 10002460
• 负责人: Dmitriy Aronov
• 金额: $ 243万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-15 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10002460
• 关键词: Address; Alzheimer' s Disease; Anatomy; Animal Model; Animals; Behavior; Behavioral; Birds; Brain; Brain region; Cells; Complex; Environment; Episodic memory; Event; Food; Goals; Hippocampal Formation; Hippocampus (Brain); Human; Knowledge; Laboratories; Location; Memory; Memory Disorders; Neurosciences; Organism; Output; Pattern; Research; Retrieval; Specialist; Structure; System; Time; Training; entorhinal cortex; experience; memory process; memory recall; neural circuit; neuromechanism; relating to nervous system

Project summary Throughout the day, the brain captures snapshots of distinct, instantaneous experiences, forming episodic memories that often last a lifetime. These types of single-shot memories require the hippocampus and the entorhinal cortex – a circuit collectively called the hippocampal formation. Disruptions of this brain region are involved in several devastating memory disorders, including Alzheimer’s disease. In spite of extensive study, we still lack basic understanding of how activity in the hippocampus implements memory functions. Neuroscience has amassed impressive knowledge about neural firing patterns in the hippocampal formation, including those of place cells and grid cells. Yet, these cells are best understood in static conditions, once an animal has learned an environment and has been extensively trained on a behavioral task. We lack a clear connection between hippocampal activity and dynamic processes of memory formation and recall. How does hippocampal activity change when a new memory is formed? How are these firing patterns interpreted by other brain regions when a memory is recalled? These questions are challenging to address because the hippocampal formation is anatomically extremely complex, and because episodic memory-guided behaviors are particularly difficult to study in standard laboratory model organisms. In this project, we seek to overcome major challenges to hippocampal research by using a unique model organism that is an extreme memory specialist – the chickadee. These birds cache thousands of food items at scattered, hidden locations in their environment and use memory to retrieve their caches later in time. Their behavior is readily produced in the lab and contains well-defined moments of memory formation (caching) and recall (cache retrieval). The repeatable and streamlined structure of food caching provides an opportunity to study neural activity underlying these memory processes. Cache memory requires the avian hippocampal formation, which is embryologically homologous to its mammalian counterpart and shares similar circuit organization. However, the avian hippocampus is anatomically simpler and has a small number of well-defined, compact, and thus easily targetable inputs and outputs. The proposed project will obtain recordings of the hippocampus while chickadees are actively caching and retrieving food. This will allow us to relate hippocampal activity to discrete memory processes and to obtain an interpretable neural signature of episodic memories. By leveraging chickadee anatomy, this project will also determine what information is conveyed by hippocampal outputs to identified targets in the brain during memory recall. The ultimate goal is to obtain a complete circuit-level understanding of episodic memory. Because of the close correspondence between our system and the mammalian hippocampus, these findings will inform other fields and will generalize to hippocampal systems in other organisms that use memory, including humans.

项目摘要 在一天中，大脑捕捉不同的瞬间经历的快照，形成情景性的 常常伴随一生的记忆这些类型的单次记忆需要海马体和 内嗅皮层--一个统称为海马结构的回路。这一大脑区域的紊乱 与包括阿尔茨海默氏症在内的几种毁灭性记忆障碍有关。尽管我们进行了广泛的研究， 仍然缺乏对海马体活动如何实现记忆功能的基本理解。 神经科学已经积累了关于海马结构神经放电模式的令人印象深刻的知识， 包括位置细胞和网格细胞。然而，这些细胞在静态条件下最好理解，一旦 动物已经学会了一种环境，并在一项行为任务上接受了广泛的训练。我们缺乏一个清晰的 海马活动与记忆形成和回忆的动态过程之间的联系。如何 海马活动在新记忆形成时会发生变化？其他人是如何解释这些放电模式的 当记忆被唤起的时候大脑的哪个区域？这些问题很难解决，因为海马 形成在解剖学上是极其复杂的，因为情景记忆引导的行为特别 难以在标准实验室模式生物中进行研究。 在这个项目中，我们试图通过使用一个独特的模型来克服海马研究的主要挑战 生物体是一个极端的记忆专家-山雀。这些鸟在它们的巢穴中 分散，隐藏的位置，并使用内存来检索他们的缓存稍后的时间。他们的 行为很容易在实验室中产生，并包含定义良好的记忆形成（缓存）时刻， 调用（缓存检索）。食物储藏的可重复和精简的结构提供了一个机会， 研究这些记忆过程背后的神经活动。高速缓存需要鸟类海马体 形成，这是胚胎同源的，其哺乳动物的对应和共享类似的电路 organization.然而，鸟类海马在解剖学上更简单， 结构紧凑，因此易于确定输入和输出的目标。 拟议中的项目将获得记录的海马体，而山雀积极缓存， 找回食物这将使我们能够将海马体活动与离散的记忆过程联系起来，并获得一个关于海马体活动的信息。 情景记忆的神经信号通过利用山雀解剖学，这个项目也将 确定在记忆过程中海马输出向大脑中识别的目标传达了什么信息 记得了最终的目标是获得完整的回路水平的情景记忆的理解。因为 我们的系统和哺乳动物海马体之间的密切联系，这些发现将告知其他 这一领域的研究将推广到其他使用记忆的生物体（包括人类）的海马系统。