CLOCK-dependent pathway in a single pair of LN <sub>d</sub> neurons instruct circadian-independent interval timing behavior
Bibliographic record
Abstract
Abstract Interval timing is a cognitive ability essential for behaviors such as mating, foraging, and decision-making, and it is distinct from circadian rhythm regulation. Despite the involvement of circadian clock genes in both interval timing and circadian rhythms, the mechanisms differentiating these functions remain unclear. Using Drosophila as a model, we demonstrate that the CLK/CYC heterodimer, but not PER/TIM, is essential for interval timing. Neuronal CLK/CYC expression is necessary and sufficient for sexual experience-dependent shorter mating duration (SMD) behavior. We identified that CLK/CYC expression in a single pair of ITP-positive LN d neurons is pivotal for SMD. These neurons are glutamatergic with output circuits to central brain regions. CLK variants lacking DNA binding motifs dissociate circadian rhythms from interval timing and sleep behaviors in these neurons. Our study uncovers a specialized circuit for interval timing and highlights the non-circadian functions of circadian clock genes. Statement of Significance This study in Drosophila demonstrates that the CLK/CYC heterodimer is crucial for interval timing, distinct from circadian rhythm regulation. The research pinpoints a specific pair of neurons that are critical for shortened mating duration behavior, and it suggests that CLK variants can influence interval timing dissociation from circadian rhythm and sleep behaviors. Highlights CLK/CYC heterodimer are essential for interval timing. Specialized mechanism of interval timing behavior revealed. Identified a pair of glutamatergic ITP-LN d neurons that independently regulate both interval timing and sleep. Revealed a novel mechanism by which CLK variants regulate sleep and interval timing. Graphical Abstract Different CLK/CYC mediate separate regulatory mechanism between circadian rhythm, sleep and interval timing in Drosophila melanogaster .
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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) | 0.001 | 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".