Rescue of NMDAR-Dependent Synaptic Plasticity in Fmr1 Knock-Out Mice
Bibliographic record
Abstract
Fragile X Syndrome (FXS) is the most common form of inherited intellectual disability and results from a loss of Fragile X mental retardation protein (FMRP). FMRP is important for mRNA shuttling and translational control and binds to proteins important for synaptic plasticity. Like many developmental disorders, FXS is associated with alterations in synaptic plasticity that may impair learning and memory processes in the brain. However, it remains unclear whether FMRP plays a ubiquitous role in synaptic plasticity in all brain regions. We report that a loss of FMRP leads to impairments in N-methyl-D-aspartate receptor (NMDAR)-dependent synaptic plasticity in the dentate gyrus (DG), but not in the cornu ammonis area 1 (CA1) subregion of the hippocampus of adult mice. DG-specific deficits are accompanied by a significant reduction in NMDAR GluN1, GluN2A, and GluN2B subunit levels and reduced serine 831 GluA1 phosphorylation specifically in this region. Importantly, we demonstrate that treatment with NMDAR co-agonists (glycine or D-serine) independently rescue impairments in NMDAR-dependent synaptic plasticity in the DG of the Fragile X mental retardation 1 (Fmr1) knockout mouse. These findings implicate the NMDAR in the pathophysiology of FXS and suggest that indirect agonists of the NMDAR may be a successful therapeutic intervention in FXS.
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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) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| 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".