Strengthened Temporal Coordination within Pre-existing Sequential Cell Assemblies Supports Trajectory Replay.

A central goal in learning and memory research is to reveal the neural substrates underlying episodic memory formation. The hallmark of sequential spatial trajectory learning, a model of episodic memory, has remained equivocal, with proposals ranging from de novo creation of compressed sequential replay from blank slate networks to selection of pre-existing compressed preplay sequences. Here, we show that increased millisecond-timescale activation of cell assemblies expressed during de novo sequential experience and increased neuronal firing rate correlations can explain the difference between post-experience trajectory replay and robust preplay. This increased activation results from an improved neuronal tuning to specific cell assemblies, higher recruitment of experience-tuned neurons into pre-existing cell assemblies, and increased recruitment of cell assemblies in replay. In contrast, changes in overall neuronal and cell assembly temporal order within extended sequences do not account for sequential trajectory learning. We propose the coordinated strengthening of cell assemblies played sequentially on robust pre-existing temporal frameworks could support rapid formation of episodic-like memory.