Activity‐dependent changes in temporal components of neurotransmission at the juvenile mouse calyx of Held synapse
Bibliographic record
Abstract
The temporal fidelity of synaptic transmission is constrained by the reproducibility of time delays such as axonal conduction delay and synaptic delay, but very little is known about the modulation of these distinct components. In particular, synaptic delay is not generally considered to be modifiable under physiological conditions. Using simultaneous paired patch-clamp recordings from pre- and postsynaptic elements of the calyx of Held synapse, in juvenile mouse auditory brainstem slices, we show here that synaptic activity (20-200 Hz) leads to activity-dependent increases in synaptic delay and its variance as well as desynchronization of evoked responses. Such changes were most robust at 200 Hz in 2 mM extracellular Ca(2+) ([Ca(2+)](o)), and could be attenuated by lowering [Ca(2+)](o) to 1 mM, increasing temperature to 35 degrees C, or application of the GABA(B)R agonist baclofen, which inhibits presynaptic Ca(2+) currents (I(Ca)). Conduction delay also exhibited slight activity-dependent prolongation, but this prolongation was only sensitive to temperature, and not to [Ca(2+)](o) or baclofen. Direct voltage-clamp recordings of I(Ca) evoked by repeated action potential train template (200 Hz) revealed little jitter in the timing and kinetics of I(Ca) under various conditions, suggesting that increases in synaptic delay and its variance occur downstream of Ca(2+) entry. Loading the Ca(2+) chelator EGTA-AM into terminals reduced the progression rate, the extent of activity-dependent increases in various delay components, and their variance, implying that residual Ca(2+) accumulation in the presynaptic nerve terminal induces these changes. Finally, by applying a test pulse at different intervals following a 200 Hz train (150 ms), we demonstrated that prolongation in the various delay components reverses in parallel with recovery in synaptic strength. These observations suggest that a depletion of the readily releasable pool of SVs during high-frequency activity may downregulate not only synaptic strength but also decrease the temporal fidelity of neurotransmission at this and other central synapses.
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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".