Rictor is involved in Ctnnd2 deletion-induced impairment of spatial learning and memory but not autism-like behaviors.

Background

The CTNND2 gene which encodes a δ-catenin protein (CTNND2) is associated with multiple severe neurological disorders. However, the specific role of CTNND2 in spatial cognition and related mechanisms remains obscure.

Methods

In this study, we generated a new line of Ctnnd2-Knock out (KO) mice with its exon2 deleted, and then characterized their behavioral phenotypes and explore the Biological mechanism.

Results

Ctnnd2-KO mice were with typical autism-like behaviors as evidenced by reduced social interaction in three-chamber sociability test, more frequent stereotypic behaviors (self-grooming), and deficits in spatial learning and memory tested by the Morris water maze. Furthermore, the expression of Rictor protein, a core component of the mTORC2 complex, was significantly decreased in the hippocampus of mutant mice. ShRNA-induced knockdown of Rictor protein in the hippocampus of both Ctnnd2-KO mice and wild-type mice exacerbated spatial learning and memory deficits but did not affect their autism-like behaviors. Mechanistically, the hippocampal CA1 neurons of Ctnnd2-KO mice showed decreased actin polymerization, postsynaptic spine density. Down-regulation of Rictor resulted in altered expression of post-synaptic proteins such as GluR1 and ELKS, but not presynaptic protein Synapsin1, implying abnormal synaptic changes in KO mice.

Conclusion

The CTNND2 gene is involved in spatial learning and memory via Rictor-mediated actin polymerization and synaptic plasticity. Our study provides a novel insight into the role and mechanisms of the Ctnnd2 gene in cognition at the molecular and synaptic levels.