Dendritic channelopathies contribute to neocortical and sensory hyperexcitability in Fmr1 −/y mice
| Autor: | Nathalie Sans, Yu Zhang, Ben A. Oostra, Andreas Frick, Guillaume Bony, Melanie Ginger, Susanna Pietropaolo, Gwen LeMasson, Jean Rossier, Isabelle Ferezou, Audrey Bonnan |
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| Přispěvatelé: | Physiopathologie du système nerveux central - Institut François Magendie, Université Bordeaux Segalen - Bordeaux 2-IFR8-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de Neurosciences Information et Complexité [Gif sur Yvette] (UNIC), Centre National de la Recherche Scientifique (CNRS), Institut de Neurobiologie Alfred Fessard (INAF), Laboratoire de Neurobiologie, Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), Department of Clinical Genetics, Erasmus MC |
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Male
Reflex Startle [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology Action Potentials Sensory system Neocortex Somatosensory system MESH: Dendrites MESH: Fragile X Mental Retardation Protein MESH: Mice Knockout 03 medical and health sciences Fragile X Mental Retardation Protein Mice MESH: Neocortex 0302 clinical medicine Calcium imaging Organ Culture Techniques MESH: Channelopathies MESH: Mice Inbred C57BL medicine Animals MESH: Animals MESH: Mice MESH: Action Potentials 030304 developmental biology Mice Knockout 0303 health sciences Sensory stimulation therapy [SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior General Neuroscience [SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences Dendrites medicine.disease FMR1 MESH: Organ Culture Techniques MESH: Male Fragile X syndrome Mice Inbred C57BL Electrophysiology medicine.anatomical_structure Channelopathies MESH: Reflex Startle Psychology Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | Nature Neuroscience Nature Neuroscience, Nature Publishing Group, 2014, 17 (12), pp.1701-1709. ⟨10.1038/nn.3864⟩ |
| ISSN: | 1097-6256 1546-1726 |
| Popis: | International audience; Hypersensitivity in response to sensory stimuli and neocortical hyperexcitability are prominent features of Fragile X Syndrome (FXS) and autism spectrum disorders, but little is known about the dendritic mechanisms underlying these phenomena. We found that the primary somatosensory neocortex (S1) was hyperexcited in response to tactile sensory stimulation in Fmr1(-/y) mice. This correlated with neuronal and dendritic hyperexcitability of S1 pyramidal neurons, which affect all major aspects of neuronal computation, from the integration of synaptic input to the generation of action potential output. Using dendritic electrophysiological recordings, calcium imaging, pharmacology, biochemistry and a computer model, we found that this defect was, at least in part, attributable to the reduction and dysfunction of dendritic h- and BKCa channels. We pharmacologically rescued several core hyperexcitability phenomena by targeting BKCa channels. Our results provide strong evidence pointing to the utility of BKCa channel openers for the treatment of the sensory hypersensitivity aspects of FXS. |
| Databáze: | OpenAIRE |
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