Increased sensitivity to sensory stimuli is a prominent feature of Fragile-X Syndrome (FXS) and other Autism Spectrum Disorders (ASD), but its underlying mechanisms are poorly understood. We found that deletion of the Fmr1 gene results in somatosensory hyper-excitability in a mouse model for FXS. Fmr1 knockout (Fmr1KO) mice required significantly less tactile information for haptic exploration, and touch-evoked whisker representations in the primary somatosensory cortex (S1) spread with increased velocity in Fmr1KO mice compared to wild-type control. At the cellular level, dendrites of S1 pyramidal neurons were hyper-excitable, facilitating the coupling of synaptic input to the generation of action potential output in these neurons. This defect was, at least in part, attributable to a dysfunction of h-channels and BKCa channels and was partially rescued by pharmacological activation of BKCa channels. These findings argue for a novel and critical role for channelopathies in the expression of sensory hyper-excitability in FXS and ASD.
37th Congress of IUPS (Birmingham, UK) (2013) Proc 37th IUPS, SA442
Research Symposium: The cellular basis of sensory hyperexcitability in the Fmr1 knockout mouse model of Fragile X Syndrome
A. Frick1, Y. Zhang1, A. Bonnan1, M. Ginger1, I. Ferezou2, J. Rossier3, B. Oostra4
1. Neurocentre Magendie, INSERM U862, Bordeaux, France. 2. CNRS UPR 3293, Gif-sur-Yvette, France. 3. CNS UMR7637, Pariz, France. 4. Erasmus MC, Rotterdam, Netherlands.
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