OSCR

Dopamine drives persistent remodelling of the maternal brain.

Overview

Authors: Jennifer C O’Chan1, Giuseppina Di Salvo1,2, Ashley M Cunningham1, Sohini Dutta1, Elizabeth Brindley1, Benjamin H Weekley1, Winnie Chen1, Rasika R Iyer1, Ethan Wan3, Cindy Zhang1, Naguib Mechawar4, Gustavo Turecki4, Ian Maze1,5,6
ORCID iDs: Jennifer C O’Chan, Giuseppina Di Salvo, Benjamin H Weekley, Winnie Chen, Rasika R Iyer, Ethan Wan, Naguib Mechawar, Gustavo Turecki, Ian Maze
  1. Nash Family Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY USA
  2. Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience (MHeNs), Maastricht University, Maastricht, The Netherlands
  3. Department of Neurobiology, University of Alabama at Birmingham, Birmingham, AL USA
  4. Douglas Institute, Department of Psychiatry, McGill University, Montreal, Quebec Canada
  5. Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY USA
  6. Howard Hughes Medical Institute, Icahn School of Medicine at Mount Sinai, New York, NY USA
Institutions: Icahn School of Medicine at Mount Sinai (United States); Maastricht University (Netherlands); University of Alabama at Birmingham (United States); McGill University (Canada); Howard Hughes Medical Institute (United States)
Journal: Nature, volume 654, issue 8118, pages 465-475
Dates: received 2 June 2025; accepted 8 April 2026; published online 20 May 2026; in print 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1038/s41586-026-10509-4 · PMID 42162419 · PMCID PMC13253353 · OpenAlex W7161761534
Open access: hybrid, a free copy (OpenAlex)
Status: code on request
Categories: genetics / omics (modality), human (organism), mouse (organism), cellular / molecular (subfield)
Methods: Connectivity, Statistics, Smoothing, state filtering, decompositions, Evoked potentials, fMRI & imaging, Spectral & time-frequency
Keywords: Molecular neuroscience, Epigenetics and behaviour
MeSH: Brain*, Dopamine*, Hippocampus*, Neuronal Plasticity*, Animals, Female, Histones, Humans, Mice, Postpartum Period, Pregnancy, Protein Processing, Post-Translational, Transcription, Genetic (* major topic)
Topic: Neurogenesis and neuroplasticity mechanisms (Developmental Neuroscience, Neuroscience), according to OpenAlex
Citations: cited by 1 paper (Europe PMC); 104 references in the paper
Research resources: RRID:SCR_025991

Abstract

Pregnancy and postpartum experiences represent transformative physiological states that impose lasting demands on the maternal body and brain, resulting in lifelong neural adaptations1–6. However, the precise molecular mechanisms that drive these persistent alterations remain poorly understood. Here we used brain-wide transcriptomic profiling to define the molecular landscape of neuroplasticity induced by reproductive experience, identifying the dorsal hippocampal formation (dHF) as a key site of transcriptional remodelling. Combining single-cell RNA sequencing with a maternal–pup separation paradigm, we additionally found that chronic postpartum stress significantly disrupts dHF adaptations by altering dopamine dynamics, leading to changes in the dopamine-dependent histone post-translational modification, H3 dopaminylation, which causally mediates downstream alterations in gene expression and behaviour. In human dorsal subiculum, a brain structure within the dHF, we uncovered conserved patterns of parity-dependent alterations in H3 dopaminylation and transcription. We further established the sufficiency of dopamine modulation in regulating these adaptations via chemogenetic suppression of dopamine release into the dHF, which recapitulated key epigenomic and behavioural features of reproductive experience in virgin female mice. In sum, our findings establish dopamine as a central regulator of parity-induced neuroadaptations in humans and mice, revealing a fundamental transcriptional mechanism by which female reproductive experience remodels the brain to sustain long-term behavioural adaptations.

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

Code

The paper says that its authors' code is available on request: it was not published with the paper, so there is nothing to verify.

Code availability

Data were analysed using publicly available software and standard pipelines, as described in the Methods. No custom code was generated for this study; however, any related analysis scripts or details are available from the corresponding authors upon reasonable request.

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

Tracing map

A tracing map links a paper to the code its authors published: this paper has none (its code is available on request), so it has no map.

Data

Datasets cited

Data availability

The genomics data generated in this study have been deposited in the National Center for Biotechnology Information Gene Expression Omnibus (GEO) database under the SuperSeries GSE298544 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE298544). Reference genomes used in this study include the mouse genome mm10 and human genome hg19. Publicly available reference datasets used for annotation included resources from the Allen Brain Map and Broad Institute, with gene annotations obtained from the UCSC Genome Browser and ENCODE blacklist regions applied where appropriate. All data supporting the findings of this study are available within the article and Supplementary Information. Related data, including raw microscopy images, are available from the corresponding authors upon reasonable request. Source data are provided with this paper.

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 2, 28 September 2026

  • Publisher: n/a → Nature Portfolio

Version 1, 28 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 13 authors, 2 keywords, 13 MeSH terms, 102 references, 1 RRID.

Cite

This paper

O’Chan, J. C., Di Salvo, G., Cunningham, A. M., Dutta, S., Brindley, E., Weekley, B. H., Chen, W., Iyer, R. R., Wan, E., Zhang, C., Mechawar, N., Turecki, G., & Maze, I. (2026). Dopamine drives persistent remodelling of the maternal brain. Nature, 654(8118), 465-475. https://doi.org/10.1038/s41586-026-10509-4

BibTeX

@article{ochan2026dopamine,
author = {O’Chan, Jennifer C and Di Salvo, Giuseppina and Cunningham, Ashley M and Dutta, Sohini and Brindley, Elizabeth and Weekley, Benjamin H and Chen, Winnie and Iyer, Rasika R and Wan, Ethan and Zhang, Cindy and Mechawar, Naguib and Turecki, Gustavo and Maze, Ian},
title = {{Dopamine drives persistent remodelling of the maternal brain}},
journal = {Nature},
year = {2026},
month = may,
volume = {654},
number = {8118},
pages = {465--475},
publisher = {Nature Portfolio},
issn = {0028-0836},
doi = {10.1038/s41586-026-10509-4},
url = {https://doi.org/10.1038/s41586-026-10509-4},
pmid = {42162419},
pmcid = {PMC13253353}
}

RIS

TY - JOUR
AU - O’Chan, Jennifer C
AU - Di Salvo, Giuseppina
AU - Cunningham, Ashley M
AU - Dutta, Sohini
AU - Brindley, Elizabeth
AU - Weekley, Benjamin H
AU - Chen, Winnie
AU - Iyer, Rasika R
AU - Wan, Ethan
AU - Zhang, Cindy
AU - Mechawar, Naguib
AU - Turecki, Gustavo
AU - Maze, Ian
TI - Dopamine drives persistent remodelling of the maternal brain
T2 - Nature
J2 - Nature
PY - 2026
DA - 2026/05/20
VL - 654
IS - 8118
SP - 465
EP - 475
SN - 0028-0836
PB - Nature Portfolio
DO - 10.1038/s41586-026-10509-4
UR - https://doi.org/10.1038/s41586-026-10509-4
LA - en
ER -

CSL-JSON

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