Locus coeruleus activation 'resets' hippocampal event representations and separates adjacent memories.

Memories reflect the ebb and flow of experiences, capturing unique and meaningful events from our lives. Using a combination of functional magnetic resonance imaging (fMRI), neuromelanin imaging, and pupillometry, we show that arousal and locus coeruleus (LC) activation transform otherwise continuous experiences into distinct episodic memories. As sequences unfold, encountering a context shift, or event boundary, triggers arousal and LC processes that predict later memory separation. Boundaries furthermore promote temporal pattern separation within left hippocampal dentate gyrus, which correlates with heightened LC responses to those same transition points. We also find that a neurochemical index of prolonged LC activation correlates with diminished arousal responses at boundaries, suggesting a connection between elevated LC output and impaired event processing. These findings align with the idea that arousal processes initiate a neural and memory 'reset' in response to significant changes, constructing the very episodes that define everyday memory.