Amplitude and Kinetics of Action Potential-Evoked Ca<sup>2+</sup>Current and Its Efficacy in Triggering Transmitter Release at the Developing Calyx of Held Synapse
Bibliographic record
Abstract
Action potentials (APs) play a crucial role in evoking Ca2+ currents (ICa) through voltage-gated calcium channels (VGCCs) and transmitter release. During development and neuromodulation, both depolarization and repolarization phases of APs change, but how such changes affect the characteristics of ICa and its efficacy at central synapses is not clear. By paired voltage-clamp recordings of ICa and excitatory postsynaptic currents (IEPSC) with pseudo-APs and real APs, we examined these issues in the developing calyx of Held synapse of postnatal mice. We found that speeding the AP depolarization rate primarily reduces the number of activated VGCCs, whereas shortening the AP repolarization phase decreases the number of activated VGCCs and accelerates their kinetics. The ICa-IESPC relationships are well predicted by the integral but not the amplitude of ICa, and exhibit development- and temperature-dependent shifts toward left, indicating an enhancement in downstream Ca2+ coupling efficacy. Cross-correlation analyses of ICa and IEPSC evoked by real APs and pseudo-APs demonstrated that AP shortening in the half-width from 0.4 ms at postnatal day 8 (P8)-P12 to 0.27 ms at P16-P18 decreases ICa integral by 36%, but increases IEPSC by 72% as a result of developmental upregulation in coupling efficacy. These counteracting actions maintain the release fraction evoked by an AP at approximately 10% of the maximal quantal output. We suggest that AP narrowing is a critical adaptation for the calyx of Held synapse to control the quantal output per AP and is likely important for the efficient use of the readily releasable pool of synaptic vesicles during high-frequency neurotransmission.
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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".