Ketamine-induced Sustained Modulation of γ-Aminobutyric Acid Type A Receptor Function in Mouse Hippocampal Neurons after Anesthesia
Bibliographic record
Abstract
BACKGROUND: Excess function of γ-aminobutyric acid type A (GABA A ) receptors that generate a tonic inhibitory conductance contributes to postanesthetic cognitive impairment. Ketamine may have postoperative cognition-sparing properties; however, whether it reduces excess GABA A receptor function is unknown. This study investigated whether ketamine prevents a sustained anesthetic-triggered increase in GABA A receptor function in vitro and mitigates postanesthetic memory deficits in vivo . METHODS: Murine hippocampal neurons and cortical astrocytes were cocultured and treated for 1 h with an injectable (etomidate) or an inhaled (sevoflurane) anesthetic, with or without ketamine. After 24 h, GABA A receptor-mediated tonic currents were recorded from neurons using whole cell patch clamp. Expression of brain-derived neurotrophic factor (BDNF) and its receptor tropomyosin receptor kinase B (TrkB) was assessed by biotinylation, Western blotting, ELISA, and quantitative polymerase chain reaction. Immunostaining was used to visualize α5 subunit-containing GABA A receptors in neurons. In vivo , adult mice were anesthetized with sevoflurane for 2 h, with or without ketamine, and recognition and spatial memory were assessed 24 and 48 h later, respectively. RESULTS: Ketamine prevented the sustained increase in GABA A receptor-mediated tonic currents triggered by etomidate and sevoflurane. This effect was independent of N -methyl- d -aspartate receptor antagonism and instead was mediated by BDNF-TrkB signaling through a GSK-3β-dependent pathway. Interestingly, ketamine did not alter BDNF levels but increased cell-surface expression of TrkB receptors and thereby facilitated BDNF-TrkB signaling. Ketamine also reduced the anesthetic-induced increase in cell-surface expression of α5 subunit-containing GABA A receptors. In vivo , ketamine prevented deficits in both recognition and spatial memory that occurred after sevoflurane anesthesia. CONCLUSIONS: Ketamine prevents the general anesthetic-induced sustained increase in GABA A receptor function by facilitating BDNF-TrkB signaling. This mechanism is associated with a mitigation of postanesthetic memory deficits in mice.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| 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) | 0.000 | 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".