The ATRX chromatin remodelling is required in astrocytes for long-term recognition memory
Bibliographic record
Abstract
Astrocytes are glial cells of the central nervous system that regulate synapse formation, maturation and elimination. Defective astrocytes can alter synaptic transmission and contribute to disease, as in monogenic neurodevelopmental disorders Rett and Fragile X syndromes. Alpha Thalassemia X-linked intellectual disability (ATR-X syndrome) is a neurodevelopmental disorder caused by mutations in the ATRX gene. We hypothesize that ATRX controls chromatin structure and the expression of astrocytic genes required for normal cognition. Here, we generated mice with tamoxifen-inducible Atrx inactivation in astrocytes (Atrxf/y;GlastCreER or ATRX aiKO,). Tamoxifen was injected from postnatal day 10 to 12 to induce Atrx deletion in astrocytes prior to maturation. Immunofluorescence staining of ATRX and cell type specific markers show that ATRX is absent in approximately 50 % of the astrocytes in the cortex and hippocampus of ATRX aiKO mice. Behavioural tests to assess different types of memory, novel object recognition and Morris water maze, show that ATRX aiKO mice exhibit long-term recognition and spatial memory deficits compared to controls. Ex vivo electrophysiology measurements, dendritic branching and spine morphology of CA1 neurons revealed reduction in synaptic function of hippocampal CA1 neurons but normal morphology. Astrocyte nuclei were purified using fluorescence activated nuclei sorting (FANS) and used for RNA-sequencing. Analysis of the transcriptome revealed altered expression of genes associated with cytoskeleton and synapse organization. Collectively, these findings demonstrate that astrocytic ATRX regulates gene expression and promote normal synaptic transmission in neighbouring hippocampal neurons, thus contributing to long-term memory processes.
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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 | 0.000 |
| 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) | 0.036 | 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".