Interneuron Desynchronization Precedes Seizures in a Mouse Model of Dravet Syndrome
Bibliographic record
Abstract
Recurrent seizures, which define epilepsy, are transient abnormalities in the electrical activity of the brain. The mechanistic basis of seizure initiation, and the contribution of defined neuronal subtypes to seizure pathophysiology, remains poorly understood. We performedin vivotwo-photon calcium imaging in neocortex during temperature-induced seizures in male and female Dravet syndrome (Scn1a+/−) mice, a neurodevelopmental disorder with prominent temperature-sensitive epilepsy. Mean activity of both putative principal cells and parvalbumin-positive interneurons (PV-INs) was higher inScn1a+/− relative to wild-type controls during quiet wakefulness at baseline and at elevated core body temperature. However, wild-type PV-INs showed a progressive synchronization in response to temperature elevation that was absent in PV-INs fromScn1a+/− mice. Hence, PV-IN activity remains intact interictally inScn1a+/− mice, yet exhibits decreased synchrony immediately before seizure onset. We suggest that impaired PV-IN synchronization may contribute to the transition to the ictal state during temperature-induced seizures in Dravet syndrome. SIGNIFICANCE STATEMENTEpilepsy is a common neurological disorder defined by recurrent, unprovoked seizures. However, basic mechanisms of seizure initiation and propagation remain poorly understood. We performedin vivotwo-photon calcium imaging in an experimental model of Dravet syndrome (Scn1a+/− mice)—a severe neurodevelopmental disorder defined by temperature-sensitive, treatment-resistant epilepsy—and record activity of putative excitatory neurons and parvalbumin-positive GABAergic neocortical interneurons (PV-INs) during naturalistic seizures induced by increased core body temperature. PV-IN activity was higher inScn1a+/− relative to wild-type controls during quiet wakefulness. However, wild-type PV-INs showed progressive synchronization in response to temperature elevation that was absent in PV-INs fromScn1a+/− mice before seizure onset. Hence, impaired PV-IN synchronization may contribute to transition to seizure in Dravet syndrome.
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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 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.002 | 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".