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

项目总结 在一天中，大脑捕捉截然不同的瞬间体验的快照，形成插曲 往往会持续一生的记忆。这些类型的单次记忆需要海马体和 内嗅皮层--一种统称为海马体结构的回路。这一大脑区域的破坏是 参与了几种毁灭性的记忆障碍，包括阿尔茨海默氏症。尽管进行了广泛的研究，我们还是 仍然缺乏对海马体活动如何实现记忆功能的基本了解。 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， 包括位置单元格和格网单元格。然而，这些细胞在静态条件下最容易理解，一旦 动物已经学会了环境，并在行为任务上接受了广泛的训练。我们缺乏一个明确的 海马区活动与记忆形成和回忆的动态过程之间的联系。何以 当形成新的记忆时，海马体的活动会发生变化吗？这些激发模式是如何被其他人解释的 记忆被唤起时的大脑区域？这些问题很难解决，因为海马体 构形在解剖学上是极其复杂的，因为情节记忆引导的行为特别 很难在标准的实验室模型生物中进行研究。 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体研究的主要挑战 一种极端记忆专家的有机体--山雀。这些鸟把数以千计的食物藏在 在他们的环境中分散、隐藏的位置，并使用内存在以后的时间检索他们的缓存。他们的 行为很容易在实验室中产生，并包含明确定义的记忆形成时刻(缓存)和 调用(缓存检索)。可重复和精简的食物缓存结构提供了一个机会 研究这些记忆过程背后的神经活动。缓存记忆需要鸟类的海马体 形成，它在胚胎上与哺乳动物的对应物同源，拥有相似的回路 组织。然而，鸟类的海马体在解剖上更简单，有少量定义明确的， 紧凑，因此很容易有针对性的投入和产出。 拟议的项目将获得海马体的录音，而山雀正在积极地缓存和 取回食物。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 情节记忆的可解释神经特征。通过利用山雀的解剖学，这个项目还将 确定在记忆过程中，海马体的输出向大脑中已识别的目标传递了什么信息 召回。最终的目标是获得对情节记忆的完整的电路水平的理解。因为 我们的系统与哺乳动物海马体之间的密切对应，这些发现将告知其他 并将推广到包括人类在内的其他使用记忆的有机体的海马体系统。

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.