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

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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.