Inserm Team "PLASTICITY OF CORTICAL CONNECTIVITY"
Inserm Unit862, "NEUROCENTRE MAGENDIE"
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In autistic children, information coming from the 5 senses – touch, hearing, sight or other stimuli – are not correctly interpreted in the brain, leading to inappropriate behaviour and sometimes uncontrollable reactions. Inserm researchers led by Andréas Frick in Inserm Unit 862 ‘Magendie Neurocentre’ have recently understood why by studying a mouse model mimicking the disorder. They have even found a molecule that could reverse these effects and restore ‘normal’ behaviour in these mice.
These findings are published in the journal Nature Neuroscience
Autistic Spectrum Disorders (ASD) affect more than 3 million people in the European Union, including about 650,000 in France. Recent estimates from the Centre for Disease Control (in the USA) suggest that one child in 68 is affected by this disorder. ASDs are neuro-developmental disorders that affect children from all ethnic and socio-economic origins, and are characterised by a spectrum of symptoms including both difficulties in social interactions and communication as well as stereotypical repetitive behaviours.
Another common aspect of neuro-developmental disorders is the problem of processing sensory information. Nearly 90% of children with ASDs are affected by different types of sensory problems. Problems of sensory interpretation derive from the fact that peripheral information, whether from touch, hearing, sight or other stimuli, are not interpreted or organised correctly in the brain, leading to inappropriate behaviour. Such problems can be extremely disabling in daily life for people affected by autism and they create a challenge for parents and teachers. For example, during a visit to the supermarket, simple fluorescent lights can be an unpleasant sensory experience. Unfortunately, alterations of sensory interpretation in these disorders and their pharmacological treatments are little studied, even if these alterations are also frequently observed in a related neuro-developmental disorder, Fragile X Syndrome.
In a study published in Nature Neuroscience, Inserm researchers (working with researchers from the French CNRS – national centre for scientific research) have shown that Fragile X mice display disorders in the manner that sensory information is processed by the neocortex, which is one of the parts of the brain responsible for sensory perception. The researchers have shown that the neocortex of these mice is hyperexcited in response to tactile sensory stimulation. They then performed a variety of detailed tests showing that this neocortical hyperexcitability is linked to the way the neurons in this region of the brain interpret sensory information. With this study, the researchers found that the function of certain ionic channels (molecules that determine the manner in which neurons process electrical signals) is altered in the dendritic compartment (the structure that interprets information and really behaves as the ‘brain’ of neurons).
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Dendritic channelopathies contribute to neocortical and sensory hyperexcitability in Fmr1−/y mice Yu Zhang1,2,7,8, Audrey Bonnan1,2,7,8, Guillaume Bony1,2,8, Isabelle Ferezou3,7, Susanna Pietropaolo4,5, Melanie Ginger1,2, Nathalie Sans1,2, Jean Rossier3,7, Ben Oostra6, Gwen LeMasson1,2 & Andreas Frick1,2 1INSERM, Neurocentre Magendie, Physiopathologie de la plasticité neuronale, U862, Bordeaux, France. 2University of Bordeaux, Neurocentre Magendie, Physiopathologie de la plasticité neuronale, U862, Bordeaux, France. 3Laboratoire de Neurobiologie, ESPCI ParisTech CNRS UMR 7637, Paris, France. 4University of Bordeaux, INCIA, Talence, France. 5CNRS, INCIA, UMR 5287, Talence, France. 6Department of Clinical Genetics, Erasmus MC, Rotterdam, the Netherlands. 7Present address: Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK (Y.Z.), Max Planck Florida Institute for Neuroscience, Jupiter, Florida, USA (A.B.), Unité de Neurosciences Information et Complexité, CNRS UPR 3293, Gif-sur-Yvette, France (I.F.), Centre de Psychiatrie et Neurosciences, INSERM U894, Université Paris Descartes, Paris, France (J.R.). 8These authors contributed equally to this work Nature Neuroscience novembre 2014