The ubiquitin ligase UBR-1 regulates the synaptic strength between the GABAergic and glutamatergic signaling
Bibliographic record
Abstract
Abstract Excitation/Inhibition (E/I) balance is carefully maintained by the nervous system. Neurotransmitter GABA has been reported to be co-released with its sole precursor, another neurotransmitter glutamate. The genetic and circuitry mechanisms to establish the balance between GABAergic and Glutamatergic signaling have not fully elucidated. C. elegans DVB is a classically defined excitatory GABAergic motoneuron that drives the expulsion step in defecation motor program. We show that in addition to UNC-47, the vesicular GABA transporter, DVB also expresses EAT-4, a vesicular glutamate transporter. UBR-1, a conserved ubiquitin ligase, regulates the DVB activity by suppressing a bidirectional inhibitory glutamate signaling. Loss of UBR-1 impairs the DVB Ca 2+ activity and the expulsion frequency. These impairments are fully compensated by the knock-down of EAT-4 in DVB. Further, glutamate-gated chloride channels GLC-3 and GLC-2/4 receive DVB’s glutamate signals to inhibit DVB and enteric muscle, respectively. These results implicate an intrinsic cellular mechanism that promotes the inherent asymmetric neural activity. We propose that the elevated glutamate in ubr-1 being the cause of the E/I shift, potentially contributes to the Johanson Blizzard Syndrome.
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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 | 0.000 |
| 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".