Fragile X mice develop sensory hyperreactivity to auditory stimuli

Fragile X syndrome is the most prevalent cause of mental retardation. It is usually caused by the transcriptional inactivation of the FMR-I gene. Alth ough the cognitive defect is the most recognized symptom of fragile X syndr ome, patients also show behavioral problems such as hyperarousal, hyperacti vity, autism, aggression, anxiety and increased sensitivity to sensory stim uli. Here we investigated whether fragile X mice (fmr-1 gene knockout mice) exhibit abnormal sensitivity to sensory stimuli. First, hyperreactivity of fragile X mice to auditory stimulus was indicated in the prepulse inhibiti on paradigm. A moderately intense prepulse tone, that suppresses startle re sponse to a strong auditory stimulus, elicited a significantly stronger eff ect in fragile X than in control mice. Second, sensory hyperreactivity of f ragile X mice was demonstrated by a high seizure susceptibility to auditory stimulation. Selective induction of c-Fos, an early-immediate gene product , indicated that seizures involve auditory brainstem and thalamic nuclei. A udiogenic seizures were not due to a general increase in brain excitability because three different chemical convulsants (kainic acid, bicuculline and pentylenetetrazole) elicited similar effects in fragile X and wild-type mi ce. These data are consistent with the increased responsiveness of fragile X pa tients to auditory stimuli. The auditory hypersensitivity suggests an abnor mal processing in the auditory system of fragile X mice, which could provid e a useful model to study the molecular and cellular changes underlying fra gile X syndrome. (C) 2001 IBRO. Published by Elsevier Science Ltd. All righ ts reserved.