Skip to Main content Skip to Navigation
Journal articles

Cognition- and circuit-based dysfunction in a mouse model of 22q11.2 microdeletion syndrome: effects of stress

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.
Complete list of metadatas

Cited literature [82 references]  Display  Hide  Download

https://www.hal.inserm.fr/inserm-02571318
Contributor : Clara Martinez Rico <>
Submitted on : Tuesday, May 12, 2020 - 5:44:34 PM
Last modification on : Monday, September 21, 2020 - 10:54:02 AM

File

s41398-020-0687-z.pdf
Publication funded by an institution

Identifiers

Collections

Citation

Anushree Tripathi, Michael Spedding, Esther Schenker, Michael Didriksen, Arnaud Cressant, et al.. Cognition- and circuit-based dysfunction in a mouse model of 22q11.2 microdeletion syndrome: effects of stress. Translational Psychiatry, Nature Pub. Group, 2020, 10 (1), pp.41. ⟨10.1038/s41398-020-0687-z⟩. ⟨inserm-02571318⟩

Share

Metrics

Record views

143

Files downloads

95