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Repeated sleep deprivation selectively reactivates hippocampal CA1 pyramidal neurons.

Overview

Authors: Yutong Wang1,2, Emily N Walsh2,3,4, Junko Kasuya1,2, Colton E Remedies5, Jon Resch1,2, Lisa C Lyons5, Ted Abel1,2
ORCID iDs: Yutong Wang, Emily N Walsh, Junko Kasuya, Colton E Remedies, Jon Resch, Lisa C Lyons, Ted Abel
  1. Department of Neuroscience and Pharmacology, Carver College of Medicine, University of Iowa, 51 Newton Road, 2-417B Bowen Science Building, Iowa City, IA 52242 USA
  2. Iowa Neuroscience Institute, Carver College of Medicine, University of Iowa, 169 Newton Road, 2312 Pappajohn Biomedical Discovery Building, Iowa City, IA 52242 USA
  3. Interdisciplinary Graduate Program in Neuroscience, 356 Medical Research Center, University of Iowa, Iowa City, IA 52242 USA
  4. Present Address: Department of Neurology, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, MO 63110 USA
  5. Program in Neuroscience, Department of Biological Science, Florida State University, 319 Stadium Drive, Tallahassee, FL 32306 USA
Institutions: University of Iowa (United States); Washington University in St. Louis (United States); Florida State University (United States)
Journal: Molecular brain, volume 19, issue 1, article 39
Dates: received 21 January 2026; accepted 21 March 2026; published online 1 April 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1186/s13041-026-01298-y · PMID 41923141 · PMCID PMC13169576 · OpenAlex W7147172507
Open access: gold, a free copy (OpenAlex)
Status: data only
Categories: mouse (organism), cellular / molecular (subfield)
Methods: Statistics
Keywords: Sleep deprivation, Hippocampus, CA1, Pyramidal neurons, c-Fos, RiboTag, fosTRAP-seq
MeSH: CA1 Region, Hippocampal*, Pyramidal Cells*, Sleep Deprivation*, Animals, Gene Expression Regulation, Male, Mice, Inbred C57BL, Phosphorylation, Proto-Oncogene Proteins c-fos, Ribosomes, RNA, Messenger, Synapses (* major topic)
Topic: Sleep and Wakefulness Research (Cognitive Neuroscience, Neuroscience), according to OpenAlex
Funding: National Institutes on Aging (5R01AG062398)
Citations: not cited yet (Europe PMC); 73 references in the paper

Abstract

Sleep supports a variety of physiological processes, ranging from metabolic to immune system homeostasis, and plays a critical role in cognition and memory. A brief period of sleep loss impairs memory, particularly hippocampus-dependent memories, alters molecular signaling, and synaptic plasticity in the hippocampus. Studies have shown that sleep deprivation (SD) alters neuronal activation as indicated by broad changes in gene expression signatures and by the increased expression of c-Fos, an immediate early gene that functions as a molecular marker of neuronal activity. In the present study, we examined hippocampal subregion-specific c-Fos induction patterns via immunohistochemical staining. We found that CA1 pyramidal neurons exhibit the most robust c-Fos induction after SD. Using an activity-driven ribosomal tagging system (c-Fos-RiboTag) and a repeated SD model, we labeled sleep deprivation activated CA1 neurons and observed a population of excitatory neurons in area CA1 that are reactivated by repeated SD. Using the c-Fos-RiboTag system that enables the isolation of ribosomes with attached mRNA from labeled neurons, we performed fosTRAP-seq and identified activity-dependent gene expression changes in c-Fos+ CA1 neurons. Our results revealed that synapse organization, protein dephosphorylation, cellular response to endogenous stimulus (such as insulin) are upregulated, whereas mRNA processing and splicing are downregulated. In summary, our study provides a detailed characterization of hippocampal neuronal activation following SD and identifies a subset of CA1 pyramidal neurons that are selectively reactivated by repeated SD. This SD-sensitive neuronal population enables investigation of molecular changes in neurons specifically impacted by sleep loss and suggests a potential connection between acute and chronic sleep loss at the cellular and molecular levels.

Supplementary Information: The online version contains supplementary material available at 10.1186/s13041-026-01298-y.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

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Data

Datasets cited

Data availability

The datasets generated and/or analyzed during the current study are available in the NCBI’s Gene Expression Omnibus repository, GEO Series accession GSE316227, [https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi? acc=GSE316227] , and DEG accession GSE156925 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE156925), [https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi? acc=GSE156925 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE156925)] . Any additional information underlying this article will be shared on reasonable request to the corresponding author.

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 1, 28 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 7 authors, 7 keywords, 12 MeSH terms, 1 funder, 72 references.

Cite

This paper

Wang, Y., Walsh, E. N., Kasuya, J., Remedies, C. E., Resch, J., Lyons, L. C., & Abel, T. (2026). Repeated sleep deprivation selectively reactivates hippocampal CA1 pyramidal neurons. Molecular brain, 19(1), 39. https://doi.org/10.1186/s13041-026-01298-y

BibTeX

@article{wang2026repeated,
author = {Wang, Yutong and Walsh, Emily N and Kasuya, Junko and Remedies, Colton E and Resch, Jon and Lyons, Lisa C and Abel, Ted},
title = {{Repeated sleep deprivation selectively reactivates hippocampal CA1 pyramidal neurons}},
journal = {Molecular brain},
year = {2026},
month = apr,
volume = {19},
number = {1},
pages = {39},
publisher = {BMC},
issn = {1756-6606},
doi = {10.1186/s13041-026-01298-y},
url = {https://doi.org/10.1186/s13041-026-01298-y},
pmid = {41923141},
pmcid = {PMC13169576}
}

RIS

TY - JOUR
AU - Wang, Yutong
AU - Walsh, Emily N
AU - Kasuya, Junko
AU - Remedies, Colton E
AU - Resch, Jon
AU - Lyons, Lisa C
AU - Abel, Ted
TI - Repeated sleep deprivation selectively reactivates hippocampal CA1 pyramidal neurons
T2 - Molecular brain
J2 - Mol Brain
PY - 2026
DA - 2026/04/01
VL - 19
IS - 1
SP - 39
SN - 1756-6606
PB - BMC
DO - 10.1186/s13041-026-01298-y
UR - https://doi.org/10.1186/s13041-026-01298-y
LA - en
ER -

CSL-JSON

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