Noradrenergic infraslow rhythm during sleep is the critical link between heart-rate dynamics and memory consolidation

Recent studies reveal the brain's arousal system continues active during slumber, with a rhythmic locus coeruleus (LC) activity influencing sleep structure and aiding memory formation. The LC discharges norepinephrine (NE) in infraslow (~0.02 Hz) pulses that regulate NREM sleep spindles. Our research reveals that heart rate (HR) variations during NREM sleep align tightly with these NE patterns, designating the LC as a primary promoter of very-low-frequency HR variability (VLF-HRV), a lesser-known autonomic signal.

Employing optogenetics, we observed that brief LC suppression dampens HR deceleration, while LC stimulation triggers rapid HR acceleration, indicating a direct LC-HR relationship during slumber that persists within a specific LC activity spectrum but falters when LC activity surges. We also discovered that infraslow HR variability serves as a cross-species indicator of spindle-driven memory processing.

In mice, the magnitude of HR decelerations during NREM correlates with spindle frequency and subsequent memory performance. Strikingly, human sleepers exhibit the same pattern: larger VLF-HR fluctuations during NREM coincide with heightened spindle generation and superior overnight memory retention. These findings elucidate a mechanism whereby regulated fluctuations in LC activity, up to a critical threshold, modulate autonomic physiology during sleep and establish infraslow HR variability as a non-invasive gauge of brainstem function and memory-enhancing slumber.

Given that LC degeneration initiates early in neurodegenerative diseases, sleep-derived HR parameters may function as a scalable signal of incipient neuromodulatory impairment.