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bioRxiv · 10.64898/2026.07.31.742126

Disrupted Developmental Trajectory of Ultrasonic Vocalizations in a Rat Model of Fragile X Syndrome

Gauthier, D. W.·Vaidya, A.·James, N.·Auerbach, B. D.
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Abstract

Communication deficits are a defining feature of autism spectrum disorder (ASD) and among the earliest detectable markers of atypical neurodevelopment. Yet how specific genetic ASD risk factors shape the developmental trajectory of vocal communication remains poorly understood. Fragile X syndrome (FXS) is the most common inherited cause of ASD, resulting from the transcriptional silencing of the FMR1 gene, and a majority of FXS individuals exhibit impaired language development and atypical vocal communication. Rodent ultrasonic vocalizations (USVs) produced during maternal isolation provide a tractable model for studying the developmental trajectory of early vocal communication in FXS. Here, we characterized isolation- induced USVs in Fmr1 knockout (KO) and littermate wildtype (WT) rats from postnatal days 3- 21 to determine whether Fmr1 mutation disrupts the acoustic structure, temporal organization, or sequential syntax of USVs across postnatal development. We found that Fmr1 KO rat pups exhibited reduced call number during the peak developmental window for isolation-induced calling (p6-p10), while acoustic structure and temporal organization were largely preserved. Network analysis of call transitions revealed that WT pups exhibited a progressive increase in syntactic complexity from p3-p10. However, this developmental trajectory was significantly altered and delayed in Fmr1 KO pups. Together, these findings demonstrate that Fmr1 mutation not only disrupts vocal production but the developmental expansion of syntactic flexibility in rats, highlighting USV syntax as a sensitive marker of atypical communicative development in FXS models.

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Gauthier, D. W., Vaidya, A., James, N., Auerbach, B. D.. 2026-08-01. Disrupted Developmental Trajectory of Ultrasonic Vocalizations in a Rat Model of Fragile X Syndrome. https://doi.org/10.64898/2026.07.31.742126

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