Nitric oxide dependence of glutamate‐mediated modulation at a vertebrate neuromuscular junction
Bibliographic record
Abstract
Recent evidence has revealed a contribution of glutamate in the stereotyped cholinergic neuromuscular transmission. Indeed, receptors, transporters and glutamate itself are present at the neuromuscular junction (NMJ) while glutamate activation of metabotropic receptors (mGluRs) decreases synaptic transmission and mediates depression through presynaptic mechanisms. However, we have shown that the mGluRs are located postsynaptically, inconsistent with the presynaptic action of glutamate. In the present study, we tested whether nitric oxide (NO) serves as a retrograde messenger mediating the distant effect of glutamate. Glutamate or an mGluR agonist [trans-(1S,3R)-aminocyclopentanedicarboxylic acid (ACPD)] failed to reduce synaptic transmission in the presence of an NOS inhibitor (3Br7NINa, 3-bromo-7-nitroindazole sodium salt). Moreover, application of 3Br7NINa precluded the effect of the mGluR antagonist MCPG [(S)-alpha-methyl-4-carboxyphenylglycine] on high-frequency-induced synaptic depression. Iontophoretic injections of BAPTA [1,2-bis(2-aminophenoxy)ethane-N,N,N'-tetraacetic acid] in muscle fibres abolished the effect of trans-ACPD on synaptic transmission and blocked the mGluR component of depression, indicating the involvement of muscular calcium in mGluR-induced depression. Also, the use of this protocol unveiled a muscular calcium-dependent potentiating pathway dependent on cyclo-oxygenase activity. In addition, local application of trans-ACPD induced an increase in NO production by muscle fibres visualized with the indicator DAF-FM (4-amino-5-methylamino-2',7'-difluorofluorescein). This was prevented by 3Br7NINa or the iontophoretic injection of BAPTA. Moreover, motor nerve stimulation (50 Hz, 30 s) induced an increase in DAF-FM fluorescence that was abolished by 3Br7NINa and MCPG. Hence, the data suggest that the production of the retrograde molecule NO depends on the postsynaptic calcium-dependent activation of nitric oxide synthase following mGluRs stimulation and is essential for the glutamatergic modulation of synaptic efficacy and plasticity at the NMJ.
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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 | 0.000 |
| 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".