Publications

Dernière publication 28/01/2020

Cognition-and circuit-based dysfunction in a mouse model of 22q11- 2 microdeleti

Genetic microdeletion at the 22q11 locus is associated with very high risk for schizophrenia. The 22q11.2 microdeletion (Df(h22q11)/+) mouse model...

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    [title] => Cognition-and circuit-based dysfunction in a mouse model of 22q11- 2 microdeleti
    [paragraph] => Cognition-and circuit-based dysfunction in a mouse model of 22q11. 2 microdeletion syndrome: effects of stress
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Authors
A Tripathi, M Spedding, E Schenker, M Didriksen et al

 Lab
Institute of Psychiatry and Neurosciences of Paris (IPNP), INSERM U1266, Pathophysiology of Psychiatric Disorders, Université de Paris, Paris, France
Journal
Translational Psychiatry
Abstract
Genetic microdeletion at the 22q11 locus is associated with very high risk for schizophrenia. The 22q11.2 microdeletion (Df(h22q11)/+) mouse model shows cognitive deficits observed in this disorder, some of which can be linked to dysfunction of the prefrontal cortex (PFC). We used behavioral (n_=_10 per genotype), electrophysiological (n_=_7 per genotype per group), and neuroanatomical (n_=_5 per genotype) techniques to investigate schizophrenia-related pathology of Df(h22q11)/+ mice, which showed a significant decrease in the total number of parvalbumin positive interneurons in the medial PFC. The Df(h22q11)/+ mice when tested on PFC-dependent behavioral tasks, including gambling tasks, perform significantly worse than control animals while exhibiting normal behavior on hippocampus-dependent tasks. They also show a significant decrease in hippocampus-medial Prefrontal cortex (H-PFC) synaptic plasticity (long-term potentiation, LTP). Acute platform stress almost abolished H-PFC LTP in both wild-type and Df(h22q11)/+ mice. H-PFC LTP was restored to prestress levels by clozapine (3_mg/kg i.p.) in stressed Df(h22q11)/+ mice, but the restoration of stress-induced LTP, while significant, was similar between wild-type and Df(h22q11)/+ mice. A medial PFC dysfunction may underlie the negative and cognitive symptoms in human 22q11 deletion carriers, and these results are relevant to the current debate on the utility of clozapine in such subjects.
BIOSEB Instruments Used
Smart 3.0 - Video Tracking System (SMART30)
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