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Updated: Jun 26, 2026
Dissecting Cell-Autonomous Function of Fragile X Mental Retardation Protein in an Auditory Circuit by In Ovo Electroporation
Published on: July 6, 2022
Expression of GAD in the Cochlear Nucleus and Superior Olivary Complex and Auditory Brainstem Response Thresholds in
Junjie Liu1, Jiaye Tang1, Datao Zou1
1Guangzhou Medical University The Second School of Clinical Medicine, Guangzhou, China.
Background:
This study investigates audiogenic seizures in Fmr1 knockout (KO) mice compared with wild-type (WT) mice across different ages. The aim was to assess auditory thresholds and examine glutamic acid decarboxylase (GAD) expression in auditory pathways to clarify the mechanisms underlying seizure susceptibility in fragile X syndrome (FXS).
Methods:
Fmr1 knockout (KO) and wild-type (WT) FVB mice of different ages were used. Audiogenic seizure susceptibility was evaluated using sound stimulation. Auditory brainstem response (ABR) testing was performed to assess auditory thresholds, and glutamic acid decarboxylase (GAD) expression in auditory-related brain regions was examined by immunohistochemistry. Statistical analyses were conducted to compare KO and WT groups.
Results:
Genetic identification confirmed Fmr1 gene knockout in all KO mice, which exhibited significantly lower seizure thresholds than WT mice (P < .05). Upon sound stimulation, KO mice displayed fear, running, and seizures with opisthotonus. Auditory brainstem response thresholds were significantly higher in KO mice at 3-4 weeks of age (P < .01), with no significant differences observed at 6-10 weeks (P > .05). Immunohistochemical analysis revealed significantly higher GAD expression in the auditory cortex, cochlear nucleus, and superior olivary complex of KO mice across all age groups (P < .01).
Conclusion:
Fmr1 KO mice exhibit age-dependent audiogenic seizures associated with transiently elevated auditory thresholds and increased GAD expression. These alterations suggest an imbalance of excitatory-inhibitory signaling within auditory circuits. Importantly, the findings also support the view that seizures in FXS are not solely the result of auditory system pathology, but rather reflect broader cortical abnormalities, including impaired inhibitory interneuron function and cortical network hyperexcitability. Emphasizing cortical contributions provides a more comprehensive explanation for seizure pathogenesis in FXS and aligns with recent evidence of cortical parvalbumin neuron degeneration in Fmr1-deficient models.
