Deficiency of Autism-Related Gene Dock4 Leads to Impaired Spatial Memory and Hippocampal Function in Mice at Late Middle Age

Guo, Daji; Yang, Xiaoman; Gao, Ming; Chen, Xiaoqing; Tang, Yanping; Shen, Lingling; Li, Keshen; Shi, Lei

doi:10.1007/s10571-022-01233-4

Cited by 2 publications

(1 citation statement)

References 58 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Experimenters were blind to the genotypes during testing. More behavioral experiments were performed following our previous protocols (Guo et al, 2021(Guo et al, , 2022Xiao et al, 2021;Yang et al, 2021c), and the detailed procedures are described as follows.…”

Section: Behavior Testsmentioning

confidence: 99%

eEF2 in the prefrontal cortex promotes excitatory synaptic transmission and social novelty behavior

et al. 2022

EMBO Reports

Self Cite

View full text Add to dashboard Cite

Regulation of mRNA translation is essential for brain development and function. Translation elongation factor eEF2 acts as a molecular hub orchestrating various synaptic signals to protein synthesis control and participates in hippocampus‐dependent cognitive functions. However, whether eEF2 regulates other behaviors in different brain regions has been unknown. Here, we construct a line of Eef2 heterozygous (HET) mice, which show a reduction in eEF2 and protein synthesis mainly in excitatory neurons of the prefrontal cortex. The mice also show lower spine density, reduced excitability, and AMPAR‐mediated synaptic transmission in pyramidal neurons of the medial prefrontal cortex (mPFC). While HET mice exhibit normal learning and memory, they show defective social behavior and elevated anxiety. Knockdown of Eef2 in excitatory neurons of the mPFC specifically is sufficient to impair social novelty preference. Either chemogenetic activation of excitatory neurons in the mPFC or mPFC local infusion of the AMPAR potentiator PF‐4778574 corrects the social novelty deficit of HET mice. Collectively, we identify a novel role for eEF2 in promoting prefrontal AMPAR‐mediated synaptic transmission underlying social novelty behavior.

show abstract

Section: Behavior Testsmentioning

confidence: 99%