Rat subicular networks gate hippocampal output activity in an <i>in vitro</i> model of limbic seizures
Bibliographic record
Abstract
Evidence obtained from human epileptic tissue maintained in vitro indicates that the subiculum may play a crucial role in initiating epileptiform discharges in patients with mesial temporal lobe epilepsy. Hence, we used rat hippocampus-entorhinal cortex (EC) slices to identify the role of subiculum in epileptiform synchronization during bath application of 4-aminopyridine (4AP, 50 microM). In these slices, fast CA3-driven interictal-like events were restricted to the hippocampal CA3/CA1 areas and failed to propagate to the EC where slow interictal-like and ictal-like epileptiform discharges were recorded. However, antagonizing GABA(A) receptors with picrotoxin (50 microM) made CA3-driven interictal activity spread to EC. Sequential field potential analysis along the CA3-CA1-subiculum axis revealed that the amplitude of CA3-driven interictal discharges recorded in the presence of 4AP only diminished within the subiculum. Furthermore, CA1 electrical stimulation under control conditions elicited little or no subicular activation and never any response in EC; in contrast, robust subicular discharges that spread to EC could be evoked after picrotoxin. Intracellular recordings indicated that potentiation by picrotoxin was associated with blockade of hyperpolarizing IPSPs in subicular cells. Finally, when surgically isolated from adjacent structures, the subiculum generated low-amplitude synchronous discharges that corresponded to an intracellular hyperpolarization-depolarization sequence, were resistant to glutamatergic antagonists, and represented the activity of synchronized interneuronal networks. Bath application of picrotoxin abolished these 4AP-induced events and in their place robust network bursting occurred. In conclusion, our study demonstrates that the subiculum plays a powerful gating role on hippocampal output activity. This function depends on GABA(A) receptor-mediated inhibition and controls hippocampal-parahippocampal interactions that are known to modulate limbic seizures.
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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 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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".