Locus coeruleus activation ‘resets’ hippocampal event representations and separates adjacent memories

Memories reflect the ebb and flow of experiences, capturing distinct 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 segment continuous experiences into discrete memories. As sequences unfold, encountering a context shift, or event boundary, triggers pupil-linked 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. Unlike transient LC effects, indirect structural and functional markers of elevated background LC activation correlate with reduced arousal-related LC and pupil responses at boundaries, suggesting that hyperarousal disrupts event segmentation. Our findings support the idea that arousal mechanisms initiate a neural and memory 'reset' in response to significant changes, fundamentally shaping the episodes that define episodic memory.