The endocannabinoid systemʼs involvement in motor development relies on cannabinoid receptors, <scp>TRP</scp> channels, and Sonic Hedgehog signaling
Bibliographic record
Abstract
The endocannabinoid system (eCS) plays critical roles in locomotor function and motor development; however, the roles of non-canonical cannabinoid receptor systems such as transient receptor potential (TRP) channels and the Sonic Hedgehog (SHH) signaling pathway in conjunction with the eCS in sensorimotor development remains enigmatic. To investigate the involvement of canonical and non-canonical cannabinoid receptors, TRP channels, and the SHH pathway in the development of sensorimotor function in zebrafish, we treated developing animals with pharmacological inhibitors of the CB1R, CB2R, TRPA1/TRPV1/TRPM8, and a smoothened (SMO) agonist, along with inhibitors of the eCS catabolic enzymes fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) during the first ~24 h of zebrafish embryogenesis. Locomotor function was examined by assessing touch-evoked escape swimming at 2 days post-fertilization. We report that FAAH inhibition had no effect on swimming while MAGL inhibition using JZL 184 reduced swimming distance and the dual FAAH/MAGL inhibitor JZL 195 impaired swimming distance and mean swimming velocity. The CB1R antagonist AM 251 prevented locomotor deficits caused by eCS perturbation but the CB2R antagonist AM 630 did not. Inhibition of TRPA1/TRPV1/TRPM8 using AMG 9090 rescued the locomotor reductions caused by FAAH/MAGL inhibition, but not by MAGL inhibition alone. The SMO agonist purmorphamine attenuated the effects of JZL 184 and JZL 195 on swimming distance, but not mean velocity. Together, these findings provide one of the first investigations examining the interactions between the eCS and its non-canonical receptor systems in vertebrate motor development.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.001 | 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) | 0.000 | 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 teacher head, 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".