PT  - JOURNAL ARTICLE
AU  - Thomas Marissal
AU  - Rodrigo F. Salazar
AU  - Cristina Bertollini
AU  - Sophie Mutel
AU  - Mathias De Roo
AU  - Ivan Rodriguez
AU  - Dominique Müller
AU  - Alan Carleton
TI  - Restoring wild type-like network dynamics and behaviour during adulthood in a mouse model of schizophrenia
AID  - 10.1101/151795
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 151795
4099  - http://biorxiv.org/content/early/2017/06/19/151795.short
4100  - http://biorxiv.org/content/early/2017/06/19/151795.full
AB  - Schizophrenia is a severely debilitating neurodevelopmental disorder. Establishing a causal link between circuit dysfunction and particular behavioural traits relevant to schizophrenia is crucial to shed new light on the mechanisms underlying the pathology. Here we studied an animal model of the 22q11 deletion syndrome, which is the highest genetic risk to develop the pathology. We report a desynchronization of hippocampal neuronal assemblies that resulted from parvalbumin interneuron hypoexcitability. Rescuing parvalbumin interneuron excitability with pharmacological or chemogenetic approaches is sufficient to restore wild type-like network dynamics and behaviour during adulthood. In conclusion, our data provide mechanistic insights underlying network dysfunction relevant to schizophrenia and demonstrate the potential of reverse engineering in fostering new therapeutic strategies to alleviate the burden of neurodevelopmental disorders.