Maternal separation recalibrates prefrontal mitochondrial function and protects against stress-induced negative cognitive bias

Overview

1. Department of Psychology, University of Cambridge, Downing St, Cambridge, CB2 3EB, UK
2. Department of Physiology, Development & Neuroscience, Downing Street, Cambridge, CB2 3EG, UK
3. Department of Psychiatry, Herschel Smith Building for Brain and Mind Sciences, University of Cambridge, CB2 0SZ, UK

Abstract

Ambiguity represents a form of uncertainty in which outcome probabilities cannot be explicitly learned, making decisions dependent on emotional states and cognitive biases. Early-life stress (ELS) increases the risk of adverse mental and physical health outcomes and alters affective processing and learning. ELS may thus affect how ambiguous information is processed, which may depend on interactions with adulthood stress (AS) and mechanistically on bioenergetic mechanisms mediated by top-down cognitive control systems within the prefrontal cortex (PFC). The present study investigated the effects of AS in rats exposed to early maternal separation (MS), a rodent model of ELS, on a task assessing cognitive bias, together with putatively accompanying alterations in PFC mitochondrial function. Cognitive bias was assessed using an ambiguous cue task (ACT) in MS and non-separated control rats tested at baseline and following repeated unpredictable mild stress during adulthood. MS did not affect baseline cognitive bias but increased response latencies. Following AS, control animals showed a significant negative shift in cognitive bias, whereas MS animals were resistant to this shift. MS was also associated with greater PFC mitochondrial respiratory capacity and uncoupling of oxidative phosphorylation following AS. These findings suggest that ELS is associated with a recalibrated phenotype that buffers against the affective consequences of later stress. Enhanced PFC mitochondrial bioenergetics may underlie this resilience, highlighting the importance of developmental context in shaping affective-cognitive responses to stress.

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

Code

No file of the authors' code could be read here: it is described below, and read at its source.

Tracing map

Proposed by the machine: these links were found in the paper and verified at the source, without human review. The map will receive a Zenodo DOI once one of the paper's authors has validated it with their ORCID.

What the map holds:

• 1 repository of the authors' code, each at its verified commit, with its license and how the link was found in the paper;
• 0 scripts, each with its path and the digest of its content;
• no match between paragraphs and code yet;
• neither the text of the paper nor the code itself.

Its JSON (tracing-map.json) is deposited on Zenodo with its DOI once the map is validated.

Data

No dataset and no data link were found in the paper.

Data availability

Data are available upon reasonable request from the corresponding author. For the purpose of open access, the authors have applied a Creative Commons Attribution (CCBY) licence to any Author Accepted Manuscript version arising from this submission.

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, 27 September 2026: the first record

Recorded: type, journal, dates, 9 authors, 7 keywords, 1 funder, 88 references.

Cite

This paper

Stupart, O., Marti-Prats, L., Holzner, L. M., Ibegbulam, S., Milton, A. L., Lawson, R. P., Murray, A. J., Velazquez-Sanchez, C., & Dalley, J. W. (2026). Maternal separation recalibrates prefrontal mitochondrial function and protects against stress-induced negative cognitive bias. Research Square (preprint). https://doi.org/10.21203/rs.3.rs-10384174/v1

The tracing map gets a citation of its own once an author has validated it and it has a DOI.

Similar papers

The papers with a page that share the most with this one: the tools found in their code, their categories, datasets, cited references and authors, the rarest counting most.

[1] doi:10.1186/s12868-026-01018-1

Combined maternal separation and limited bedding-nesting increase goal tracking, delay discounting, and impulsive action, and moderate sign-tracking-perseverance associations in male rats.

Journal: BMC neuroscience

In common: rat, 2 references

[2] doi:10.21203/rs.3.rs-10117408/v1

Individualised mapping of living human brain mitochondria by MRI reveals signatures of bioenergetic defects.

Journal: Research Square (preprint)

In common: cellular / molecular, 2 references

[3] doi:10.1186/s13041-026-01304-3

Genome-wide mapping of stress-responsive lncRNA, uc.104, reveals the chromatin-mediated regulation of stress and plasticity-related genes in the hippocampus of chronic restraint rats.

Journal: Molecular brain

In common: rat, cellular / molecular, 1 reference

[4] doi:10.1162/netn.a.546 [code]

Cortical similarity networks in the rat brain: Postnatal development and sensitivity to early life stress.

Journal: Network neuroscience (Cambridge, Mass.)

In common: rat, 1 reference

[5] doi:10.1126/sciadv.aeg2327

Top-down corticostriatal control of adaptive restraint during motivational conflict.

Journal: Science advances

In common: rat, 1 reference

[6] doi:10.3389/fnmol.2026.1844602

Prenatal and neonatal housing conditions affect anxiety-like behavior in adulthood in rats and interact with brain-derived neurotrophic factor (BDNF) Val66Met to alter expression of BDNF and stress markers in the ventral hippocampus.

Journal: Frontiers in molecular neuroscience

In common: rat, 1 reference

[7] doi:10.1186/s40035-026-00565-1

Plant-derived mitochondria mitigate aging-related neurodegeneration by reprogramming microglial mitochondrial energy metabolism.

Journal: Translational neurodegeneration

In common: cellular / molecular, 1 reference

[8] doi:10.1038/s41467-026-74753-y [code]

A human-specific microRNA controls the timing of excitatory synaptogenesis.

Journal: Nature communications

In common: cellular / molecular, 1 reference

[9] doi:10.3390/biom16040570

Variecolactone, a Natural PDE4 Inhibitor from Marine-Derived <i>Talaromyces</i> sp. ZSD-1, Alleviates Amyloid-β Accumulation and mtDNA Dyshomeostasis via cAMP-PKA-CREB Signaling Pathway.

Journal: Biomolecules

In common: cellular / molecular, 1 reference

[10] doi:10.1111/acel.70470

Serum-Derived Extracellular Vesicles as Biological Indicator of Mobility Resilience in Older Adults.

Journal: Aging cell

In common: cellular / molecular, 1 reference

Contribute

The authors of this paper can claim it, correct its record and validate its tracing map, and the maintainers of its code (its owner, or a public member of its organization) correct what it says of their repository; anyone signed in can ask for its removal. Every request goes to OSCR's own machine, which answers it; your account page follows them.

Request its removal

To ask OSCR to remove this record, the copies of its authors' scripts or its tracing map, use the removal request page: signed in, you say who you are, what to remove and why, then review and confirm the request. Published rules decide every request (how).

Discussion: questions and error reports about this paper and its code, from signed-in readers and its authors. It opens with sign-in.

Reproductions: reports from readers who ran the authors' code: what they reproduced, with which environment, commit and data. It opens with sign-in.

Activity: what happens around this paper: new versions of its record, its map's validation, discussions and reproductions. It opens with sign-in.