Neuronal hypertrophy dampens neuronal intrinsic excitability and stress responsiveness during chronic stress
Bibliographic record
Abstract
KEY POINTS: The hypothalamic-pituitary-adrenal (HPA) axis habituates to repeated stress exposure. We studied hypothalamic corticotropin-releasing hormone (CRH) neurons that form the apex of the HPA axis in a mouse model of stress habituation using repeated restraint. The intrinsic excitability of CRH neurons decreased after repeated stress in a time course that coincided with the development of HPA axis habituation. This intrinsic excitability plasticity co-developed with an expansion of surface membrane area, which increased a passive electric load and dampened membrane depolarization in response to the influx of positive charge. We report a novel structure-function relationship for intrinsic excitability plasticity as a neural correlate for HPA axis habituation. ABSTRACT: Encountering a stressor immediately activates the hypothalamic-pituitary-adrenal (HPA) axis, but this stereotypic stress response also undergoes experience-dependent adaptation. Despite the biological and clinical importance, how the brain adjusts stress responsiveness in the long term remains poorly understood. We studied hypothalamic corticotropin-releasing hormone neurons that form the apex of the HPA axis in a mouse model of stress habituation using repeated restraint. Using patch-clamp electrophysiology in acute slices, we found that the intrinsic excitability of these neurons substantially decreased after daily repeated stress in a time course that coincided with their loss of stress responsiveness in vivo. This intrinsic excitability plasticity co-developed with an expansion of surface membrane area, which increased a passive electric load, and dampened membrane depolarization in response to the influx of positive charge. Multiphoton imaging and electron microscopy revealed that repeated stress augmented ruffling of the plasma membrane, suggesting an ultrastructural plasticity that may efficiently accommodate the membrane area expansion. Overall, we report a novel structure-function relationship for intrinsic excitability plasticity as a neural correlate for adaptation of the neuroendocrine stress response.
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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 | 0.001 |
| 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".