Regulation of a synaptic pathway in Autism spectrum disorders
Bibliographic record
Abstract
Neurexin-LRRTM is a key synapse organizing complex, which controls the molecular composition and functional properties of excitatory synapses. Both neurexins and LRRTMs are implicated in cognitive disorders such as autism spectrum disorders (ASD) and schizophrenia. Lack of LRRTM4 in mice reduces excitatory synapse number and function by up to 35% across brain regions and compromises several forms of synaptic plasticity. Here, we investigated the functional significance of neurexin interaction with LRRTMs. We found that LRRTMs have a differential requirement for protein domains of neurexin but require the heparan sulfate (HS) modification to induce presynaptic differentiation. Also, we generated a series of mutations in LRRTM4 substituting closely spaced stretches of positively charged residues with alanine. We found that the modified HS chains of neurexin binds to positive residues within the LRR 5-8 domains of LRRTM4. Our study reveals a novel mode of interaction between neurexins and LRRTMs which is essential for the development of excitatory synapses.
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How this classification was reachedexpand
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 | 0.001 | 0.001 |
| 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 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 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 itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, 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".