Xavier Leinekugel et al. in Neuropsychopharm.

Maria Isabel Carreno-Munoz, Fabienne Martins, Maria Carmen Medrano, Elisabetta Aloisi, Susanna Pietropaolo, Corentin Dechaud, Enejda Subashi, Guillaume Bony, Melanie Ginger, Abdelmalik Moujahid, Andreas Frick & Xavier Leinekugel (2017). Potential involvement of impaired BKCa channel function in sensory defensiveness and some behavioral disturbances induced by unfamiliar environment in a mouse model of FXS.  Neuropsychopharmacology, Jul 19 (in press)https://www.ncbi.nlm.nih.gov/pubmed/28722023

Xavier Leinekugel  du Team ‘Cortical plasticity’, Neurocentre Magendie

---

In Fragile X Syndrome (FXS), sensory-hypersensitivity and impaired habituation is thought to result in attention overload and various behavioral abnormalities in reaction to the excessive and remanent salience of environment-features that would normally be ignored. This phenomenon, termed sensory defensiveness, has been proposed as the potential cause of hyperactivity, hyperarousal, and negative reactions to changes in routine that are often deleterious for FXS patients. However, the lack of tools for manipulating sensory-hypersensitivity has not allowed the experimental testing required to evaluate the relevance of this hypothesis. Recent work from our group has shown that BMS-204352, a BKCa channel agonist, was efficient to reverse cortical hyper-excitability and related sensory hypersensitivity in the Fmr1-KO mouse model of FXS. In the present study, we report that exposing Fmr1-KO mice to novel or unfamiliar environments resulted in multiple behavioral perturbations, ranging from hyperactivity to impaired nest building and excessive grooming of the back. Reversing sensory hypersensitivity with the BKCa channel agonist BMS-204352 prevented these behavioral abnormalities in Fmr1-KO mice. These results are in support of the sensory defensiveness hypothesis, and confirm BKCa as a potentially relevant molecular target for the development of drug medication against FXS / ASD.