0145 CATAPLEXY PRODUCES MUSCLE PARALYSIS BY RECRUITING THE REM SLEEP CIRCUIT
Bibliographic record
Abstract
Cataplexy, a symptom of narcolepsy, is defined as the abrupt and uncontrollable onset of skeletal muscle paralysis during wakefulness. It has been hypothesized that cataplexy results from inappropriate intrusion of REM sleep paralysis into wakefulness. The mechanism of muscle paralysis in cataplexy is unclear, but is thought to result from pathological recruitment of the subcoeruleus nucleus (SubC) that generates REM sleep paralysis. Here, we show that activation of SubC neurons promotes cataplexy in narcoleptic mice, whereas, its inhibition reduces it. We bilaterally infused 400nL of an AAV harboring a modified G-protein coupled receptor (AAV-HSYN-hm3D(Gq)-mCherry or AAV-HSYN-hm4D(Gi)-mCherry) or an inert fluorophore (AAV-HSYN-GFP) into the SubC region of narcoleptic mice. Animals were instrumented for EEG and EMG recordings. Administration of clozapine-N-oxide (CNO, 0.5mg/kg and/or 5mg/kg) was used to activate/inhibit SubC neurons expressing modified receptors. Sleep/wake data was analyzed for 3 hours following CNO administration. SubC activation in narcoleptic mice triggered a dose dependent increase in the number of cataplexy episodes (0.5mg/kg CNO: hm3D(Gq) x=25 ± 4.1, n=9 vs. control x=2 ± 0.6, n=3, p<0.05; 5mg/kg CNO: hm3D(Gq) x=64 ± 12.4, n=9 vs. control x= 3.3 ± 0.9, n=3, p<0.05) and in overall time spent in cataplexy (0.5mg/kg CNO: hm3D(Gq) x=14.6 ± 2.9% vs. control x= 0.6 ± 0.14%, p<0.05; 5mg/kg CNO: hm3D(Gq) x=33.3 ± 6.9% vs. control x= 0.9 ± 0.34%, p<0.05). Consistent with our hypothesis, inhibition of SubC neurons resulted in a 58% reduction in cataplexy (n=4, p<0.05). These results support our long-standing hypothesis that a REM sleep mechanism modulates muscle paralysis during cataplexy. This research was funded by the Canadian Institutes of Health Research (CIHR), the Natural Sciences and Engineering Research Council of Canada (NSERC), and the Ontario Graduate Scholarship (OGS).
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.002 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| 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; both teacher heads agree on what is shown here.
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".