SCRAPPER Selectively Contributes to Spontaneous Release and Presynaptic Long-Term Potentiation in the Anterior Cingulate Cortex
Bibliographic record
Abstract
SCRAPPER is an E3 ubiquitin ligase expressed in presynaptic terminals, neural cell body, and dendrites of the hippocampus and cortex, which is coded by theFBXL20gene. SCRAPPER is known to regulate synaptic transmissions and long-term potentiation (LTP) in the hippocampus, but no report is available for the cortex. Here we show genetic evidence for critical roles of SCRAPPER in excitatory transmission and presynaptic LTP (pre-LTP) of the anterior cingulate cortex (ACC), a critical cortical region for pain, anxiety, and fear. Miniature and spontaneous releases, but not evoked release, of glutamate were significantly increased in SCRAPPER knock-out (SCR-KO) mice. Interestingly, SCRAPPER selectively contributes to the increases of frequency and amplitude. The pre-LTP in the ACC was completely blocked in SCR-KO mice. Our results thus provide direct evidence for SCRAPPER in both spontaneous release and pre-LTP in the ACC and reveal a potential novel target for treating anxiety-related disease. SIGNIFICANCE STATEMENTThe anterior cingulate cortex (ACC) plays critical roles in pain, anxiety, and fear. Peripheral injury induces long-term changes in synaptic transmission in the ACC. Our recent study found that a presynaptic form of LTP (pre-LTP) in the ACC contributes to chronic pain-induced anxiety. Here, we show that SCRAPPER plays a critical role in ACC pre-LTP as well as synaptic transmission.
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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".