Noradrenergic-dependent restoration of visual discrimination in a mouse model of <i>SYNGAP1</i> -related disorder
Bibliographic record
Abstract
Abstract Atypical sensory processing in neurodevelopmental disorders contributes to cognitive, social, and behavioural disruptions, yet underlying neurophysiological mechanisms remain unclear. Using a mouse model of SYNGAP1 haploinsufficiency (HET), a common monogenic cause of intellectual disability and autism, we investigated visual processing deficits. Syngap HET mice exhibited impaired behavioural visual discriminability, associated with reduced coding precision for visual stimuli in the primary visual cortex (V1). Notably, intrinsic properties of V1 neurons and visual responses under anaesthesia were unaltered, suggesting behavioural state-dependent disruptions in awake Syngap HET mice. Supporting this, both mice and individuals with SYNGAP1 haploinsufficiency exhibited larger pupil size during visual stimulation, implicating neuromodulatory dysfunction. Targeting noradrenergic tone systemically with an α 2 -adrenergic receptor agonist restored V1 coding precision in Syngap HET mice. Our findings reveal neuromodulatory dysregulation as a novel mechanism underlying sensory disruptions in SYNGAP1 -related disorder, highlighting potential therapeutic targets for addressing sensory impairments in neurodevelopmental disorders.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 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".