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-1 gene. Although the cognitive defect is the most recognized symptom of fragile X syndrome, patients also show behavioral problems such as hyperarousal, hyperactivity, autism, aggression, anxiety and increased sensitivity to sensory stimuli. 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 inhibition paradigm. A moderately intense prepulse tone, that suppresses startle response to a strong auditory stimulus, elicited a significantly stronger effect in fragile X than in control mice. Second, sensory hyperreactivity of fragile 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. Audiogenic 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 mice. These data are consistent with the increased responsiveness of fragile X patients to auditory stimuli. The auditory hypersensitivity suggests an abnormal processing in the auditory system of fragile X mice, which could provide a useful model to study the molecular and cellular changes underlying fragile X syndrome.
Chen
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L
Department of Pharmacology, Weill Medical College of Cornell University, 1300 York Avenue, LC 522, New York, NY 10021, USA.
Toth
M
M
D000161:Acoustic Stimulation; D000818:Animals; D001522:Behavior, Animal; D001933:Brain Stem / Q000378:metabolism; D003292:Convulsants; D051860:Fragile X Messenger Ribonucleoprotein 1; D005600:Fragile X Syndrome / Q000523:psychology*; D020022:Genetic Predisposition to Disease; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics; D009433:Neural Inhibition; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D016601:RNA-Binding Proteins; D012016:Reference Values; D013216:Reflex, Startle; D012640:Seizures / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism; D013788:Thalamus / Q000378:metabolism
D003292:Convulsants; D051860:Fragile X Messenger Ribonucleoprotein 1; D009419:Nerve Tissue Proteins; D016760:Proto-Oncogene Proteins c-fos; D016601:RNA-Binding Proteins; C497684:Fmr1 protein, mouse