Restoring wild-type-like CA1 network dynamics and behavior during adulthood in a mouse model of schizophrenia

Article Article scientifique Article Restoring wild-type-like CA1 network dynamics and behavior during adulthood in a mouse model of schizophrenia eng 2018 author Marissal Thomas 790713 author Salazar Toro Rodrigo 831124 author Bertollini Cristina 806014 author Mutel Sophie 843705 author De Roo Mathias 629721 author Rodriguez Ivan 28183 author Muller Dominique 26488 author Carleton Alan 676577 1412-1420 10.1038/s41593-018-0225-y 1097-6256 http://www.nature.com/articles/s41593-018-0225-y Schizophrenia is a severely debilitating neurodevelopmental disorder. Establishing a causal link between circuit dysfunction and particular behavioral traits that are relevant to schizophrenia is crucial to shed new light on the mechanisms underlying the pathology. We studied an animal model of the human 22q11 deletion syndrome, the mutation that represents the highest genetic risk of developing schizophrenia. We observed a desynchronization of hippocampal neuronal assemblies that resulted from parvalbumin interneuron hypoexcitability. Rescuing parvalbumin interneuron excitability with pharmacological or chemogenetic approaches was sufficient to restore wild-type-like CA1 network dynamics and hippocampal-dependent behavior during adulthood. In conclusion, our data provide insights into the network dysfunction underlying schizophrenia and highlight the use of reverse engineering to restore physiological and behavioral phenotypes in an animal model of neurodevelopmental disorder. Mental disorder Schizophrenia Parvalbumin interneuron Desynchonization Dewey 590 Dewey 616.8 44 Département de génétique et évolution 162 53 Département de neurosciences fondamentales 21A false 536 Groupe Carleton Alan (neurosciences fondamentales) 876 820 Groupe Rodriguez Nature Neuroscience 21 10 df6a8c86-963a-457b-bd06-7934f190cef4 Article (Published version) Restricted marissalNatNeuro2018withSI.pdf 11937290 application/pdf restrictedAccess Faculté des sciences / Section de biologie / Département de génétique et évolution Faculté de médecine / Section de médecine fondamentale / Département de neurosciences fondamentales

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Restoring wild-type-like CA1 network dynamics and behavior during adulthood in a mouse model of schizophrenia	Nature Neuroscience			2018	631	11

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Salazar Toro, Rodrigo