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

Jacques Micheau*, Alice Vimeney, Elisabeth Normand, Christophe Mulle, Gernot Riedel

*Corresponding author for this work

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1059-1069
Number of pages11
JournalHippocampus
Volume24
Issue number9
Early online date30 Apr 2014
DOIs
Publication statusPublished - Sep 2014

Keywords

  • Autism spectrum disorder
  • Behavioral flexibility
  • GluK2 KO mice
  • Pattern separation/completion
  • Social behavior
  • Spatial learning
  • Water maze

ASJC Scopus subject areas

  • Cognitive Neuroscience

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