The exocytosis regulator complexin controls spontaneous synaptic vesicle release in a CAPS-dependent manner at C. elegans excitatory synapses
Bibliographic record
Abstract
The balance between synaptic excitation and inhibition (E/I) is essential for coordinating motor behavior, yet the differential roles of exocytosis regulators in this balance are less understood. In this study, we investigated the roles of 2 conserved exocytosis regulators, complexin/CPX-1 and CAPS/UNC-31, in excitatory versus inhibitory synapses at Caenorhabditis elegans neuromuscular junctions. cpx-1 null mutants exhibited a marked increase in spontaneous release specifically at excitatory synapses, alongside an unequal reduction in excitatory and inhibitory evoked release. A clamping-specific knockin mutant, cpx-1(Δ12), which preserved evoked release, also showed a biased enhancement in excitatory spontaneous release. Conversely, the unc-31 null mutation, while maintaining normal spontaneous release, displayed a more pronounced reduction in evoked release at excitatory synapses. Notably, we found that CPX-1's clamping function is dependent on UNC-31 and is sensitive to external Ca2+. Pull-down experiments confirmed that CAPS/UNC-31 does not directly interact with complexin, implying an indirect regulatory mechanism. Moreover, complexin regulates activity-dependent synaptic plasticity, which is also UNC-31 dependent. The unexpected role of CAPS/UNC-31 in the absence of CPX-1 clamping function may underpin the synaptic E/I balance and coordinated behavioral outputs in different species.
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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 | 0.000 | 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) | 0.000 | 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".