Investigating Cell-Types and Pathways Responsible for Increased Seizure Generation in a Model of Neurofibromatosis Type 1
Bibliographic record
Abstract
Neurofibromatosis type 1 (NF1) is a neurocutaneous disorder where individuals have increased prevalence of seizures and epilepsy. Some cases are secondary to NF1-related intracranial lesions, but others may be related to the genetic mutation itself through unknown mechanisms. Decreased neurofibromin in NF1 causes increased mTOR and ERK signaling and interneuron overactivity. We hypothesized: 1) decreased levels of neurofibromin in interneurons is sufficient to increase seizure susceptibility and 2) pharmacological inhibition of mTOR will normalize the increased seizure susceptibility. Contrary to our hypothesis, we found decreased neurofibromin in vGlut2+ cells increased seizure susceptibility. While mTOR inhibition decreased susceptibility in Nf1+/- mice, there was a similar effect from vehicle alone (DMSO) which correlated with decreased S6 and Akt activity in the cortex and hippocampus. Our findings suggest increased seizure susceptibility in NF1 is driven at least in part by vGlut2+ excitatory neurons. Additional testing will need to be conducted to properly evaluate the role of mTOR inhibition on seizure susceptibility in NF1.
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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) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 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) | 0.003 | 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".