Impaired hippocampus-dependent spatial flexibility and sociability represent autism-like phenotypes in GluK2 mice.

Jacques Micheau, Alice Vimeney, Elisabeth Normand, Christophe Mulle, Gernot Riedel
Hippocampus. 2014-04-30; 24(9): 1059-1069
DOI: 10.1002/hipo.22290

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1. Hippocampus. 2014 Sep;24(9):1059-69. doi: 10.1002/hipo.22290. Epub 2014 Apr 30.

Impaired hippocampus-dependent spatial flexibility and sociability represent
autism-like phenotypes in GluK2 mice.

Micheau J(1), Vimeney A, Normand E, Mulle C, Riedel G.

Author information:
(1)Institut de Neurosciences Cognitives et Intégratives d’Aquitaine, Université
de Bordeaux, CNRS, UMR 5287, 33 405, Talence, Cedex, France.

Autism is a complex neurodevelopmental disorder with high heritability. grik2
(which encodes the GluK2 subunit of kainate receptors) has been identified as a
susceptibility gene in Autism Spectrum Disorders (ASD), but its role in the core
and associated symptoms of ASD still remains elusive. We used mice lacking GluK2
(GluK2 KO) to examine their endophenotype with a view to modeling aspects of
autism, including social deficits, stereotyped and repetitive behavior and
decreased cognitive abilities. Anxiety was recorded in the elevated plus maze,
social behavior in a three-chamber apparatus, and cognition in different water
maze protocols. Deletion of the GluK2 gene reduced locomotor activity and
sociability as indicated by the social interaction task. In addition, GluK2 KO
mice learnt to locate a hidden platform in a water maze surrounded by a curtain
with hanging cues faster than wild-type mice. They maintained a bias toward the
target quadrant when some of these cues were removed, at which point wild-types
orthogonalized the behavior and showed no memory. However, GluK2 KO mice were
impaired in spatial reversal learning. These behavioral data together with
previously published electrophysiology showing severe anomalies in CA3 network
activity, suggest a computational shift in this network for enhanced propensity
of pattern completion that would explain the loss of behavioral flexibility in
GluK2 KO mice. Although a single mutation cannot recapitulate the entire core
symptoms of ASD, our data provide evidence for glutamatergic dysfunction
underlying a number of social- and cognition-related phenotypes relevant to ASD.

© 2014 Wiley Periodicals, Inc.

DOI: 10.1002/hipo.22290
PMID: 24753134 [Indexed for MEDLINE]

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