A Calcium-Dependent Feedback Mechanism Participates in Shaping Single NMDA Miniature EPSCs
Bibliographic record
Abstract
NMDA receptors (NMDARs) are highly calcium-permeable and are negatively regulated by intracellular calcium during prolonged exposure to agonist. We have investigated whether calcium-mediated feedback occurs during transient exposure to glutamate during single synaptic events. Examination of miniature EPSCs (mEPSCs) indicated that the decay kinetics of the NMDAR component was markedly slowed by the intracellular perfusion of exogenous calcium buffers (BAPTA or Fluo-3). In contrast, the AMPA receptor component of the miniature EPSC was unaffected. Slow on-rate calcium buffers, such as EGTA, did not alter kinetics of the NMDAR component of the mEPSC. Addition of exogenous fast calcium buffers did not slow the decay kinetics of glutamate-evoked currents mediated by NR1/NR2A heteromers expressed in HEK 293 cells, suggesting that the effect we observed in neurons may be specific to processes associated with synaptically activated receptors. Trial-to-trial amplitude variability of miniature calcium transients mediated by NMDARs increased with the injection of exogenous calcium buffers, suggesting that the amplitude of synaptic calcium transients are maintained at a rather constant level by a calcium-mediated feedback mechanism.
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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 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
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".