Long-term impact of early life stress on serotonin connectivity
Bibliographic record
Abstract
Abstract Chronic childhood stress is a prominent risk factor for developing mood disorders, yet mechanisms underlying this association remain unclear. Serotonin (5-HT) plays a crucial role in neurodevelopment and vulnerability to mood disorders. Maintenance of optimal 5-HT levels during early postnatal development is critical for the maturation of brain circuits. Developmental stress can alter the serotonin system, leading to chronic behavioral deficits. Yet, our understanding of the long-term impact of early life stress (ELS) on serotonin connectivity remains incomplete. Using a mouse model of chronic developmental stress, we sought to determine how ELS impacts brain-wide serotonin activity and behavior in adulthood. We established that adult female and male mice exposed to ELS during the first postnatal week show heightened anxiety-like behavior. Using in vivo fiber photometry and c-fos dependent activity mapping, we found that ELS enhances susceptibility to acute stress by disrupting the brain-wide functional connectivity of the raphe nucleus and the activity of dorsal raphe serotonin neuron population, in conjunction with a profound increase in the orbitofrontal cortex (OFC) activity. We further identified that 5-HT release in the medial OFC during environmental challenge is disrupted in mice exposed to ELS. Optogenetic stimulation of 5-HT terminals in the mOFC elicited an anxiolytic effect in ELS mice in a sex-dependent manner. Our findings hold significant insight into the mechanisms underlying long-term brain connectivity deficits induced by ELS, with potential implications for developing targeted stimulation-based treatments for affective disorders that arise from early life adversities.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot 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.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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 source (direct Gemma or distilled Codex), 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".