Temporal lobe epileptiform activity following systemic administration of 4‐aminopyridine in rats
Bibliographic record
Abstract
PURPOSE: The K(+) channel blocker 4-aminopyridine (4AP) induces epileptiform synchronization in brain slices maintained in vitro without interfering with γ-aminobutyric acid (GABA)A receptor-mediated inhibition and, actually, even enhancing it. The hypothesis that similar electrographic epileptiform patterns occur in vivo following systemic 4AP injection was tested here. METHODS: Sprague-Dawley rats (n = 13) were implanted with bipolar electrodes aimed at the hippocampal CA3 region, entorhinal cortex, subiculum, dentate gyrus, and amygdala. They were then injected with a single dose of 4AP (4-5 mg/kg, i.p.), and video-monitoring/electroencephalography (EEG) recordings were performed. KEY FINDINGS: 4AP induced convulsive or nonconvulsive seizures in 12 of 13 rats, along with generalized fascicular twitching, wet-dog shakes, and myoclonic jerks. On EEG, we observed in 7 (58.3%) of 12 animals long-lasting interictal spikes from the subiculum before the occurrence of the first seizure. Once seizures had started, interictal spikes occurred in all areas with no fixed site of origin. Most seizures (41/60, 68.3%) were characterized by a low-voltage fast-activity onset pattern and were convulsive (48/60, 80%). 4AP also induced highly rhythmic theta (6-11 Hz) oscillations in CA3 and entorhinal cortex before seizure occurrence. SIGNIFICANCE: Our study shows that systemic 4AP administration in vivo can enhance theta oscillations and induce slow interictal spikes and low-voltage fast-onset seizures similar to those reported in brain slices. We propose that these effects may reflect, at least in part, enhanced GABAA receptor-mediated inhibition as reported in in vitro studies.
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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 | 0.001 | 0.000 |
| 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 | 0.001 |
| 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".