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Directed cell-type recruitment during consolidation of a remote memory

Zeidler, Z.; Yu, A. L.; Seong, M. P.; Hundley, R.; DeNardo, L. A.

2025-06-15 neuroscience
10.1101/2025.06.13.659562 bioRxiv
Show abstract

Memories are consolidated into a distributed neocortical network for long-term storage. Long-term memory retrieval relies on cells that are active during learning and undergo necessary plasticity. However, remote memory retrieval activates a broader circuit, with learning-activated cells representing only a small subset. What are the rules and cell-types governing memory trace reorganization? We identified a class of prefrontal projection neurons that are gradually recruited to a memory trace through synaptic activity of learning-activated cells. This population, which projects to the temporal association area (TEa), progressively strengthens its encoding of memory-induced behaviors, mirroring increases in TEa activity. Notably, the prefrontal-TEa pathway is required for remote but not recent memory retrieval. Our findings reveal a cell type-specific mechanism underlying memory trace reorganization during consolidation.

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