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Record W7117107842 · doi:10.1038/s41380-025-03391-5

Homeostatic scaling ensures behavioural stability during corticosterone negative feedback

2025· article· en· W7117107842 on OpenAlexafffund
Neilen P. Rasiah, Tamás Füzesi, Ewandson L. Lameu, Nicolas Landgraf, David Rosenegger, Spencer P. Loewen, Toni-Lee Sterley, Ibukun Akinrinade, Thomas L. Kash, Wilten Nicola, Núria Daviu, Jaideep S. Bains

Bibliographic record

VenueMolecular Psychiatry · 2025
Typearticle
Languageen
FieldNeuroscience
TopicStress Responses and Cortisol
Canadian institutionsUniversity of TorontoOntario Brain InstituteUniversity Health NetworkUniversity of GuelphUniversity of Calgary
FundersCIHR Skin Research Training CentreBrain and Behavior Research Foundation
KeywordsNegative feedbackHomeostasisCorticosteroneGlutamate receptorHypothalamusIn vivoSynaptic scalingPositive feedbackScaling

Abstract

fetched live from OpenAlex

Maintaining appropriate behavioral and physiological responses in the face of challenge is essential for survival. The persistent increase in corticosteroids (CORT) during chronic stress blunts the endocrine response to any subsequent stressors. But the impact of prolonged CORT on behaviors that promote survival in the face of an acute stress is not well understood. Here we used an aerial predator threat model combined with in vivo calcium imaging, whole-cell electrophysiology, chemogenetics and computational modeling to evaluate the effects of short and long-term CORT. We show that in the short term, the activity of the corticotropin releasing hormone neurons of the paraventricular nucleus of the hypothalamus (CRHPVN) and innate defensive behaviors that rely on these cells, are sensitive to the negative feedback effects of CORT. In response to long-term increases in CORT, however, behaviors recover, even though intrinsic CRHPVN activity remains low. This escape from negative feedback requires local, homeostatic scaling of glutamate synapses that overcomes the inhibitory effects of CORT. This scaling is sufficient to maintain the output of this system in vivo and preserves innate defensive responses to threat. We propose that homeostatic synaptic scaling functions as a local adaptive mechanism to preserve the reliability of essential survival circuits during times of chronic stress.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.001
Threshold uncertainty score0.003

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.020
GPT teacher head0.273
Teacher spread0.253 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations0
Published2025
Admission routes2
Has abstractyes

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