The Calcium-Permeable AMPA Receptor Blocker IEM-1460 Increases the Intensity of Epileptiform Activity in the Entorhinal Cortex of Mice in vitro
Bibliographic record
Abstract
Abstract Epilepsy is a common neurological disorder characterized by spontaneous episodes of abnormal synchronized neuronal activity. Calcium-permeable AMPA receptors (CP-AMPARs) are hypothesized to be a promising target for pharmacological intervention in epilepsy because they play a significant role in the potentiation of glutamatergic synapses. In this study, we investigated the effects of CP-AMPAR blockade on the development of epileptiform activity in mouse entorhinal cortex slices using the selective blocker IEM-1460. Epileptiform activity was induced by 4-aminopyridine-containing perfusing solution with increased potassium ion concentration and decreased magnesium ion concentration. To register the membrane potential of neurons of deep layers of the entorhinal cortex, the whole-cell patch-clamp method was used. The activity of both pyramidal neurons and inhibitory interneurons was recorded. The simultaneous registration of two cells of the aforementioned types demonstrated that interneuron activity is predominant prior to an ictal discharge. Pharmacological blockade of CP-AMPARs resulted in an increase in the frequency of GABAergic preictal discharges and an increase in the duration of ictal activity. Thus, blockade of CP-AMPARs has a pronounced proepileptic effect that is not associated with a decrease in the activity of inhibitory interneurons. These results suggest that the proepileptic effect of CP-AMPARs blockade may be due to an increase in the probability of generation of short bursts of activity preceding and constituting the ictal discharge.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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".