Forebrain Acetylcholine Modulates Isoflurane and Ketamine Anesthesia in Adult Mice
Bibliographic record
Abstract
BACKGROUND: Cholinergic drugs are known to modulate general anesthesia, but anesthesia responses in acetylcholine-deficient mice have not been studied. It was hypothesized that mice with genetic deficiency of forebrain acetylcholine show increased anesthetic sensitivity to isoflurane and ketamine and decreased gamma-frequency brain activity. METHODS: Male adult mice with heterozygous knockdown of vesicular acetylcholine transporter in the brain or homozygous knockout of the transporter in the basal forebrain were compared with wild-type mice. Hippocampal and frontal cortical electrographic activity and righting reflex were studied in response to isoflurane and ketamine doses. RESULTS: The loss-of-righting-reflex dose for isoflurane was lower in knockout (mean ± SD, 0.76 ± 0.08%, n = 18, P = 0.005) but not knockdown (0.78 ± 0.07%, n = 24, P = 0.021), as compared to wild-type mice (0.83 ± 0.07%, n = 23), using a significance criterion of P = 0.017 for three planned comparisons. Loss-of-righting-reflex dose for ketamine was lower in knockout (144 ± 39 mg/kg, n = 14, P = 0.006) but not knockdown (162 ± 32 mg/kg, n = 20, P = 0.602) as compared to wild-type mice (168 ± 24 mg/kg, n = 21). Hippocampal high-gamma (63 to 100 Hz) power after isoflurane was significantly lower in knockout and knockdown mice compared to wild-type mice (isoflurane-dose and mouse-group interaction effect, F[8,56] = 2.87, P = 0.010; n = 5 to 6 mice per group). Hippocampal high-gamma power after ketamine was significantly lower in both knockout and knockdown mice when compared to wild-type mice (interaction effect F[2,13] = 6.06, P = 0.014). The change in frontal cortical gamma power with isoflurane or ketamine was not statistically different among knockout, knockdown, and wild-type mice. CONCLUSIONS: These findings suggest that forebrain cholinergic neurons modulate behavioral sensitivity and hippocampal gamma activity during isoflurane and ketamine anesthesia.
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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 | 0.000 | 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".