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Record W4414770672 · doi:10.1101/2025.10.01.679602

Molecular Logic of Cell Diversity and Circuit Connectivity in the REM Sleep Hub

2025· preprint· en· W4414770672 on OpenAlexafffund
Sara Katherine Pintwala, Jimmy J. Fraigne, Brittany J Dugan, Elda Arrigoni, John Peever, Patrick M. Fuller

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 ResearchNational Institutes of Health
KeywordsGlutamatergicPeriaqueductal grayPopulationBrainstemVentral tegmental areaNerve netMidbrainOptogeneticsSleep (system call)

Abstract

fetched live from OpenAlex

ABSTRACT The complexity of the brain arises from the diversity of its circuits and the molecular heterogeneity of the cells that compose them. A mechanistic understanding therefore requires mapping cellular identity and connectivity at single-cell resolution. Here we define the cellular taxonomy of the murine sublaterodorsal tegmental nucleus (SLD), a critical hub for REM sleep, using single-nucleus RNA sequencing. We identified all major brain cell classes, with oligodendrocytes as the most abundant, and resolved seventeen transcriptionally distinct neuronal groups defined by neurotransmitters, neuromodulators, and neuropeptides, each with unique molecular signatures. Projection-specific analysis further revealed that glutamatergic subpopulations targeting the ventrolateral periaqueductal gray (vlPAG) and ventral medulla are molecularly distinct, marked by characteristic receptor motifs. Strikingly, we provide the first direct evidence that SLD GLUT neurons innervate the vlPAG. This newly uncovered SLD GLUT→vlPAG pathway represents a previously unrecognized circuit node for REM sleep regulation, with the potential to act as a REM-OFF population suppressing it. Together, these findings establish a transcriptionally resolved atlas of the SLD, reveal the molecular logic of its circuit connectivity, and nominate candidate molecular actuators of REM sleep control, opening new avenues for dissecting how brainstem circuits orchestrate REM state and its transitions.

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 score0.001
Threshold uncertainty score0.002

Distilled classifier scores by category (both heads)

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

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.

Opus teacher head0.041
GPT teacher head0.249
Teacher spread0.209 · 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→