Interplay between Synchronization of Multivesicular Release and Recruitment of Additional Release Sites Support Short-Term Facilitation at Hippocampal Mossy Fiber to CA3 Pyramidal Cells Synapses
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Bibliographic record
Abstract
Synaptic short-term plasticity is a key regulator of neuronal communication and is controlled via various mechanisms. A well established property of mossy fiber to CA3 pyramidal cell synapses is the extensive short-term facilitation during high-frequency bursts. We investigated the mechanisms governing facilitation using a combination of whole-cell electrophysiological recordings, electrical minimal stimulation, and random-access two-photon microscopy in acute mouse hippocampal slices. Two distinct presynaptic mechanisms were involved in short-term facilitation, with their relative contribution dependent on extracellular calcium concentration. The synchronization of multivesicular release was observed during trains of facilitating EPSCs recorded in 1.2 mM external Ca(2+) ([Ca(2+)]e). Indeed, covariance analysis revealed a gradual augmentation in quantal size during trains of EPSCs, and application of the low-affinity glutamate receptor antagonist γ-D-glutamylglycine showed an increase in cleft glutamate concentration during paired-pulse stimulation. Whereas synchronization of multivesicular release contributed to the facilitation in 1.2 mM [Ca(2+)]e, variance-mean analysis showed that recruitment of more release sites (N) was likely to account for the larger facilitation observed in 2.5 mM [Ca(2+)]e. Furthermore, this increase in N could be promoted by calcium microdomains of heterogeneous amplitudes observed in single mossy fiber boutons. Our findings suggest that the combination of multivesicular release and the recruitment of additional release sites act together to increase glutamate release during burst activity. This is supported by the compartmentalized spatial profile of calcium elevations in boutons and helps to expand the dynamic range of mossy fibers information transfer.
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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 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.001 |
| 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 it