Cav3.1 T‐Type Calcium Channel Acts as a Gateway for <scp>GABAergic</scp> Excitation in the Medial Prefrontal Cortex That Leads to Chronic Psychological Stress Responses in Mice
Bibliographic record
Abstract
ABSTRACT Aim The molecular mechanisms of chronic stress‐induced psychiatric disorders, including depression, remain unknown. The current study aimed to assess the role of Cav3.1 T‐type calcium channels as a gateway for the chronic stress‐induced activation of parvalbumin (PV)‐positive gamma‐aminobutyric acidergic (GABAergic) neurons in the medial prefrontal cortex (mPFC) of mice. Methods The function of the Cav3.1 T‐type calcium channel in the mouse mPFC following chronic stress was investigated using behavioral tests, electrophysiological analyses, transcriptome analyses, and optogenetic approaches. Results Cav3.1‐knockout (Cav3.1−/−) mice were resistant to chronic stress‐induced depressive‐like behaviors induced by repeated forced‐swimming test or tail‐suspension test. Immunohistochemical analysis revealed that Cav3.1 was predominantly localized in PV‐positive GABAergic neurons in the mPFC. Based on transcriptomic and electrophysiological analyses, the excitatory–inhibitory (E–I) balance was disrupted by the chronic stress‐induced activation of PV‐positive GABAergic neurons in the mPFC of wild‐type (WT) mice, but not in that of Cav3.1−/− mice. Optogenetic control of PV‐positive GABAergic neurons in the mPFC revealed that they played a pivotal role in depressive‐like behaviors. The administration of TTA‐A2, a selective T‐type calcium channel antagonist, reduced chronic stress‐induced depressive‐like behaviors. Conclusion The Cav3.1 T‐type calcium channel acts as a gateway for the activation of GABAergic neurons in the mPFC of mice, thereby eliciting chronic psychobiological stress responses.
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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 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.002 | 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".