Axonal ER Ca <sup>2+</sup> Release Enhances Miniature, but Reduces Activity-Dependent Glutamate Release in a Huntington Disease Model
Bibliographic record
Abstract
Abstract Action potential-independent (miniature) neurotransmission occurs at all chemical synapses, but remains poorly understood, particularly in pathological contexts. Spontaneous release of Ca 2+ from the axonal endoplasmic reticulum (ER) is thought to facilitated miniature neurotransmission, and aberrant ER Ca 2+ handling is notably implicated in the progression of Huntington’s disease (HD) and other neurodegenerative diseases. Here, we report elevated glutamate-mediated miniature synaptic event frequencies in YAC128 (HD-model) cortical neurons, which pharmacological experiments suggest is mediated by enhanced spontaneous ER Ca 2+ release. Calcium imaging using an axon-localized sensor revealed slow action potential (AP)-independent axonal Ca 2+ waves, which were more common in YAC128 cortical neurons. Conversely, spontaneous axonal ER Ca 2+ release was associated with reduced AP-dependent axonal Ca 2+ events and consequent glutamate release. Together, our results suggest spontaneous release of axonal ER Ca 2+ stores oppositely regulates activity-dependent and -independent neurotransmitter release in HD, with potential implications for the fidelity and plasticity of cortical excitatory signaling.
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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) | 0.002 | 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".