Evidence map›Paper›PMID 42663441›Full record

ArticleeLife2026

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

Sofie S Jacobsen, Allison B Morehouse, Pin-Chun Chen, Yi Qian, Ryszard S Gomolka, Mie Andersen, Maiken Nedergaard, Sara C Mednick, Celia Kjaerby

Abstract read
In one paragraph

Article in eLife, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Arousal state modulates human hippocampal ripples.bioRxiv : the preprint server for biology · 2026
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors.

Sofie S JacobsenCenter for Translational Neuromedicine, University of Copenhagen, Copenhagen, Denmark.ORCID https://orcid.org/0000-0002-2689-4212
Allison B MorehouseDepartment of Cognitive Sciences, University of California Irvine, Irvine, United States.ORCID https://orcid.org/0000-0002-2097-4625
Pin-Chun ChenDepartment of Cognitive Sciences, University of California Irvine, Irvine, United States.ORCID https://orcid.org/0000-0002-4221-4918
Yi QianDepartment of Neuroscience, University of Copenhagen, Copenhagen, Denmark.ORCID https://orcid.org/0009-0000-1187-1694
Ryszard S GomolkaCenter for Translational Neuromedicine, University of Copenhagen, Copenhagen, Denmark.ORCID https://orcid.org/0000-0001-9797-1062
Mie AndersenCenter for Translational Neuromedicine, University of Copenhagen, Copenhagen, Denmark.ORCID https://orcid.org/0000-0002-6978-585X
Maiken NedergaardCenter for Translational Neuromedicine, University of Copenhagen, Copenhagen, Denmark.ORCID https://orcid.org/0000-0001-6502-6031
Sara C Mednick *Department of Cognitive Sciences, University of California Irvine, Irvine, United States.ORCID https://orcid.org/0000-0002-0906-3097
Celia Kjaerby *Center for Translational Neuromedicine, University of Copenhagen, Copenhagen, Denmark.ORCID https://orcid.org/0000-0003-1106-9217

Funding

Viral Tool Development Core: Visualization and manipulation of brain fluid dynamics by recombinant viral vectorsU19NS128613 · NINDS · UNIVERSITY OF ROCHESTER · PI Laura Diane Lewis · 2022 to 2026
$13.6M
The glymphatic system at the crossroad of integrative health approaches inchronic painR01AT011439 · NCCIH · UNIVERSITY OF ROCHESTER · PI NEDERGAARD, MAIKEN · 2021 to 2025
$3.1M
CRCNS: Waste-clearance flows in the brain measured using physics-informed neural networkR01AT012312 · NCCIH · UNIVERSITY OF ROCHESTER · PI Douglas H Kelley · 2022 to 2026
$1.6M
The Pharmacological Enhancement of Sleep for Memory ImprovementR01AG046646 · NIA · UNIVERSITY OF CALIFORNIA RIVERSIDE · PI MEDNICK, SARA CAROLE · 2014 to 2018
$1.5M
Alzheimer's Association VCID-UMD-26-1530489Cure Alzheimer's Fund 3101-00282BDanmarks Frie Forskningsfond 2100-00018BLundbeck Foundation 2025-1486Lundbeck Foundation R386-2021-165Lundbeck Foundation R413-2022-622Lundbeck Foundation R471-2024-458Marie Curie HORIZON-MSCA-2022-PF-01-01Marie Curie SEP-210878699NCCIH NIH HHS R01 AT011439NCCIH NIH HHS R01 AT012312NIA NIH HHS R01 AG046646NIH HHS R01AT011439NIH HHS R01AT012312NIH HHS R01AT012702NIH HHS U19NS128613NINDS NIH HHS U19 NS128613Novo Nordisk Fonden NNF20OC0066419Office of Naval Research N00014-14-1-0513Simons Foundation 811237
6 · The paper itself

Abstract

Recent work shows that the brain's arousal system remains active during sleep, with rhythmic locus coeruleus (LC) activity shaping sleep architecture and supporting memory consolidation. The LC releases norepinephrine (NE) in infraslow (~0.02 Hz) bouts that gate NREM sleep spindles. Here, we demonstrate that heart rate (HR) fluctuations during NREM are tightly phase-locked to these NE rhythms, identifying the LC as a key driver of very-low-frequency HR variability (VLF-HRV), an understudied autonomic signal. Using optogenetics, transient LC inhibition blunts HR slowing, whereas LC activation produces rapid HR acceleration, demonstrating a direct LC-HR relationship during sleep that is maintained across a defined range of LC activity levels but breaks down when LC activity becomes excessive. We further show that infraslow HR variability is a cross-species marker of spindle-dependent memory processing. In mice, the amplitude of HR decelerations during NREM correlates with spindle activity and subsequent memory performance. Remarkably, human sleepers show the same pattern: stronger VLF-HR fluctuations during NREM correspond to increased spindle expression and better overnight memory retention. These findings reveal a mechanistic pathway through which graded changes in LC activity, up to a critical level, modulates autonomic physiology during sleep and identify infraslow HR variability as a non-invasive marker of brainstem function and memory-promoting sleep. Because LC degeneration occurs early in neurodegenerative disease, sleep-derived HR metrics may provide a scalable indicator of emerging neuromodulatory dysfunction.

Indexed as

Heart RateLocus CoeruleusMemory ConsolidationNorepinephrineSleepAdultAnimalsFemaleHumansMaleMiceMice, Inbred C57BLNorepinephrineheart rate variabilityhumaninfraslowlocus coeruleusmemorymouseneurosciencesleep

Identifiers

PMID42663441
PMCPMC13524380

What OpenQuestion holds

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Read underepoch 390

Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.