Fragile X mice develop sensory hyperreactivity to auditory stimuli

• Published in: Neuroscience Vol. 103; no. 4; pp. 1043 - 1050
• Main Authors: Chen, L, Toth, M
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.01.2001; Elsevier
• Subjects: Acoustic Stimulation; Animals; audiogenic seizure; Behavior, Animal; Biological and medical sciences; Brain Stem - metabolism; c-Fos; Chromosome fragility (bloom syndrome, ataxia telangiectasia, fanconi anemia, x-linked mental retardation...); Convulsants; FMRP; Fragile X Mental Retardation Protein; fragile X syndrome; Fragile X Syndrome - psychology; Genetic Predisposition to Disease; Medical genetics; Medical sciences; Mice; Mice, Knockout - genetics; Nerve Tissue Proteins - genetics; Neural Inhibition; prepulse inhibition; Proto-Oncogene Proteins c-fos - metabolism; Reference Values; Reflex, Startle; RNA-Binding Proteins; Seizures - chemically induced; Seizures - genetics; Seizures - metabolism; Thalamus - metabolism; IC, inferior colliculus; PIL, posterior intralaminar nucleus; MGM, medial part of the geniculate nucleus; WT, wild-type; FMRP; fragile X syndrome; FMRP, fragile X mental retardation protein; c-Fos; prepulse inhibition; KO, knockout; PTZ, pentylenetetrazole; PAG, periaqueductal grey; audiogenic seizure; DNLL, dorsal nucleus of lateral lemniscus; Chromosome fragility; Nervous system diseases; Vertebrata; Mammalia; Acoustic stimulus; Hyperreactivity; Mouse; Animal; Rodentia; Fragile X syndrome; Audiogenic epilepsy
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/S0306-4522(01)00036-7

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.