Stress History Modulates Corticotropin-Releasing Factor Neurons to Establish Resilience
Bibliographic record
Abstract
Background: Cumulative stress is a major risk factor for developing major depressive disorder (MDD), but not everyone experiencing chronic stress develops MDD. In those who do not, it is unclear at what point or by what mechanism a trajectory of stable resiliency emerges. Methods: Utilizing a 10-day repeated social defeat stress (RSDS) model for MDD, we observed that a critical period between 7 and 10 daily defeats marks the phenotypical divergence of resilient from susceptible male mice. Cell-type selective electrophysiology, chemogenetics, optogenetics, and RNA quantification were used to investigate the nature of stress effects on neuroadaptation in the oval nucleus of the bed nucleus of the stria terminalis (BNSTov) required to determine resilience. Results: ) neurons of the BNSTov displayed a sustained increased firing rate in resilient but not susceptible mice. This neurophysiological adaptation was self-sustaining, but only after 7 critical stress exposures, indicating that the process of developing resilience is dependent on stress history. Conclusions: Our study reveals a novel process by which individuals may persist in the face of adversity by way of stress-provoked activation, not inhibition of a key CRF limbic region that establishes a pathway to resilience.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.003 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.002 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.005 | 0.002 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
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".