Exploring Behavioral and Neural Dynamics of Social Interactions during the Juvenile Stage in a Mouse Model of Fragile X Syndrome
Bibliographic record
Abstract
Abstract Introduction Fragile X Syndrome (FXS), caused by Fmr1 mutations, is linked to cognitive and behavioral differences, including altered social interactions. Most mouse studies focus on adults, despite human research showing critical developmental changes in childhood and adolescence. We examined social behavior in juvenile male and female Fmr1 knockout (KO) mice as well as heterozygous (HET) females. We further assessed cortical activity in KO females to better understand early phenotypes. Methods Juvenile mice of both sexes and genotypes were paired in same-sex, novel dyads for 10-minute interactions. Key social behaviors such as head, anogenital, and body sniffing, and physical touch, as well as distance travelled, were analyzed with a marker-less tracking software. Frontal-parietal EEG recordings were collected from wild-type (WT) and KO females in home cage and social contexts to analyze power spectra across frequency bands. Results HET and KO females engaged in more frequent but shorter interaction events compared to WT females, with HET females showing the highest counts. Males displayed similar trends when comparing KO and WT. Males engaged in overall higher interaction events than females. EEG analyses revealed altered oscillatory activity in KO females compared to WT females, especially within theta, alpha, and beta bands, most prominently during the early interaction phase. Locomotor activity correlated weakly with head/anogenital sniffing but more strongly with body sniffing and touch. Discussion These findings suggest that Fmr1 -related differences in juvenile social behavior are sex-dependent and associated with cortical oscillatory changes. Characterizing these early phenotypes in both sexes allows us to further understand FXS development and informs potential routes for early intervention. Key Points Fragile X Syndrome (FXS), the leading inherited cause of autism, is associated with disruptions in social behavior. While social phenotypes are relatively well described in adult mouse models of FXS, juvenile manifestations remain poorly understood. Social behavior was assessed in juvenile male and female Fmr1 knockout (KO), heterozygous (HET, female only), and wildtype (WT) mice, and frontal-parietal EEG recordings were collected from WT and KO females. HET and KO females exhibited more frequent but shorter social interactions than WT females, with HET showing the greatest number of events. Males showed similar patterns when comparing KO and WT. Males engaged in higher overall interaction events than females. EEG recordings revealed altered oscillatory activity in KO compared to WT females, most pronounced during the early phase of social encounter. These findings reveal sex- and genotype-dependent differences in juvenile social behavior and cortical activity, highlighting the importance of studying juvenile development 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) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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 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".