Fragile X mice develop sensory hyperreactivity to auditory stimuli
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Animals
FMRP-KO mice1 on the FVB (FVB/NJ-Fmr1tm1Cgr) and mixed FVB/129 (FVB,129P-Fmr1tm1Cgr) background as well as FVB wild-type (WT) mice (FVB/NJ) were purchased from The Jackson Laboratory (Bar Harbor, ME). Male mice were used in all experiments because fragile X is an X-linked disorder and affects more males than females. All animal experiments were carried out according to the NIH animal care guidelines (NIH Publications No. 80-23). All efforts were made to minimize animal suffering and to use only
Increased prepulse inhibition of the acoustic startle response in fragile X mice
Prepulse inhibition of audiogenic startle is a phenomenon in which a weak prestimulus (prepulse) suppresses the response to a startle stimulus.9., 16., 19., 30., 36. Prepulse inhibition is mediated by a complex forebrain circuitry. As Fig. 1A shows, the baseline startle response was slightly lower (by 14%) in fragile X than in WT mice (KO mice: n=14; WT mice: n=16; P=0.0486; independent Student’s t-test). A more prominent difference was observed between the two genotypes in prepulse inhibition.
Increased behavioral responsiveness of fragile X mice to auditory stimulus
The major finding of this report is the hyperreactivity of fragile X mice to auditory stimuli. Abnormalities were detected in fragile X mice in prepulse inhibition and audiogenic seizure susceptibility.
Prepulse inhibition in fragile X mice, compared to control mice, was increased by 96 and 56% when 75 and 85 dB prestimulus was used, respectively. Prepulse inhibition of acoustic startle involves the activation of a forebrain gating circuitry that presumably allows prestimulus processing, while
Acknowledgements
This work was supported by grant R01NS34151 from the National Institute of Health to M.T.
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