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Record W4412437548 · doi:10.1101/2025.07.10.664050

GABA neurons in the sublaterodorsal tegmental (SLD) nucleus suppress wakefulness in wild-type and narcoleptic mice

2025· preprint· en· W4412437548 on OpenAlexafffund
Hanhee Lee, Jimmy J. Fraigne, John Peever

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2025
Typepreprint
Languageen
FieldNeuroscience
TopicSleep and Wakefulness Research
Canadian institutionsUniversity of Toronto
FundersNatural Sciences and Engineering Research Council of CanadaCanadian Institutes of Health Research
KeywordsWakefulnessVentral tegmental areaNeuroscienceNarcolepsySleep (system call)NucleusBiologyElectroencephalographyDopamineComputer scienceNeurology

Abstract

fetched live from OpenAlex

SUMMARY The sleep-wake cycle is generated by competing neural circuits that control the oscillation between wakefulness, rapid eye movement (REM) sleep, and non-REM (NREM) sleep. While the sublaterodorsal tegmental nucleus (SLD) is recognized for its role in REM sleep generation, the functional contribution of its GABAergic neurons (SLD GABA ) to sleep-wake regulation remains poorly understood. Here, we found that SLD GABA neurons function as a suppressor of wakefulness in both wild-type and narcoleptic mice. Optogenetic silencing of SLD GABA neurons rapidly induced robust wakefulness, while enhancing cortical and motor activity. Conversely, optogenetic activation of these neurons suppressed wakefulness and promoted NREM sleep. We found that SLD GABA neurons project extensively to wake-promoting brain regions, providing an anatomical basis for their wake-suppressing effects. Importantly, we discovered that SLD GABA neurons play a pathological role in narcolepsy: their activation in orexin-deficient mice triggered characteristic sleep attacks—rapid intrusions of NREM sleep during active wakefulness— while silencing these neurons rescued animals from both sleep attacks and cataplexy. Collectively, these findings establish SLD GABA neurons as a key regulator of arousal state transitions and identify them as a novel therapeutic target for the treatment of narcolepsy.

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 machine prediction

Teacher imitation

Not 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.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.002
Threshold uncertainty score0.007

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.000
Science and technology studies0.0000.001
Scholarly communication0.0000.000
Open science0.0000.001
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0020.001

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.

Opus teacher head0.027
GPT teacher head0.261
Teacher spread0.234 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

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".

Quick stats

Citations0
Published2025
Admission routes2
Has abstractyes

Explore more

Same venuebioRxiv (Cold Spring Harbor Laboratory)→Same topicSleep and Wakefulness Research→French-language works237,207→