Ketamine Prevents a Persistent Increase in α5 GABAA Receptor Activity Induced by General Anesthetic Drugs
Bibliographic record
Abstract
GABAA receptors mediate two distinct forms of inhibition: phasic inhibition and tonic inhibition. In the hippocampus, tonic inhibition is mainly mediated by extrasynaptic α5 subunit-containing GABAA receptors, and sustained overexpression of these receptors contributes to cognitive deficits and mood disorders. Recently, ketamine, a NMDA receptor antagonist, was shown to prevent postoperative cognitive deficits and exert long-lasting antidepressant effects in patients. Given this relationship, we hypothesize that ketamine prevents a persistent increase in α5 subunit-containing GABAA receptor activity. Using whole-cell patch-clamp recordings, we show for the first time that ketamine prevents this overactivity in mouse hippocampal neurons in vitro. Furthermore, this effect is mediated by key proteins implicated in ketamine’s antidepressant actions including BDNF and GSK3β, but not by inhibition of NMDA receptors. Interestingly, ketamine acts through both neurons and astrocytes to prevent this overactivity. Our study provides a novel mechanism for the cognition-sparing and antidepressant properties of ketamine.
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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) | 0.003 | 0.001 |
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".