Glutamatergic synaptic deficits in the prefrontal cortex of the Ts65Dn mouse model for Down syndrome
Bibliographic record
Abstract
Abstract Down syndrome (DS), the most common form of intellectual disability, is a chromosomal disorder caused by having all or part of an extra chromosome 21, leading to intellectual disability. Contrary to the extensive research on the Ts65Dn mouse model of DS in the hippocampus, the synaptic foundation of prefrontal cortex (PFC) malfunction in individuals with DS, including working memory deficits, remains largely unclear. A previous study on mBACtgDyrk1a mice, which overexpress the Dyrk1a gene, showed that this overexpression negatively impacts spine density and synaptic molecular composition, causing synaptic plasticity deficits in the PFC. By comparing Ts65Dn mice, which overexpress multiple genes including Dyrk1a , and mBACtgDyrk1a mice, we aimed to better understand the role of different genes in DS. Results from electrophysiological experiments (i.e., patch-clamp and extracellular field potential recordings ex vivo) in Ts65Dn PFC male mice revealed modifications of intrinsic properties in layer V/VI pyramidal neurons and the synaptic plasticity range. Thus, long-term depression was abolished in Ts65Dn, while synaptic or pharmacological long-term potentiation were fully expressed in Ts65Dn mice. These results, illustrating the phenotypic divergence between the polygenic Ts65Dn model and the monogenic mBACtgDyrk1a model of DS, highlight the complexity of the pathophysiological mechanisms responsible for the neurocognitive symptoms of DS.
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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 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 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".