Locus coeruleus microcircuitry processes periaqueductal gray inputs into distinct outputs for regulation of pain and anxiety
Bibliographic record
Abstract
The locus coeruleus (LC) is a modularly organized heterogeneous structure that projects to various CNS regions to modulate a range of physiological and pathophysiological processes, including anxiety and pain. However, there are conflicting results on the role of LC activity in pain states. In particular, how the LC integrates inputs from upstream structures such as the ventrolateral periaqueductal gray (vlPAG) to regulate descending control of peripheral pain signals remains to be elucidated. Here, we used genetic cell-type-specific targeting of vlPAG to LC projections, optogenetics, electrophysiology, calcium imaging, and behavior assessment to define how this pathway modulates pain and anxiety-like behavior in mice with neuropathic pain. We show that glutamatergic and GABAergic vlPAG inputs into the LC differentially regulate pain and anxiety-like behavior through specific processing in the LC and the surrounding peri-LC region. Our results provide key insights into how the LC modulates critical behavioral outputs.
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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 | 0.001 |
| Scholarly communication | 0.001 | 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".