Cholinergic signaling in the forebrain regulates peripheral inflammation
Bibliographic record
Abstract
The brain regulates physiological functions integral to survival. Relatively little is known about the brain neuronal regulation of peripheral immune function. Brain cholinergic signals have been implicated in controlling peripheral inflammation, but specific insight is lacking. Here, utilizing neuron‐and receptor‐specific approaches, we studied the role of forebrain cholinergic signaling and the M1 muscarinic acetylcholine receptor (M1 mAChR) in the regulation of peripheral inflammation. Forebrain‐specific Cre‐ lox P‐based ablation of the vesicular acetylcholine transporter (required for synaptic acetylcholine release) and vagotomy abolished the suppression of serum TNF by the centrally‐acting cholinergic drug galantamine in murine endotoxemia. Basal forebrain cholinergic neurons innervate areas with abundant M1 mAChR localization. Enhancement of acetylcholine action on the brain M1 mAChR with the selective positive allosteric modulator benzyl quinolone carboxylic acid (BQCA) suppressed serum TNF levels in endotoxemia. Peripheral administration of the centrally‐acting BQCA also suppressed TNF levels and improved survival in endotoxemia, effects abolished in M1 mAChR KO mice. Optogenetic stimulation of basal forebrain cholinergic neurons in the medial septum reduced serum TNF in endotoxemic mice as compared to sham stimulation. These findings provide novel insights into brain regulation of peripheral inflammation and are of interest for developing new brain‐based treatments for inflammatory conditions. Support or Funding Information This work was supported by the following grants from the National Institute of General Medical Sciences, NIH: RO1GM089807 (to VAP and KJT) and RO1GM057226 (to KJT).
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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".