As elegant structures designed for neural communication, synapses are the building bricks of our mental functions. Recently, many studies have pointed out that synaptic protein-associated mutations may lead to dysfunctions of social cognition.
Dlgap2, which encodes one of the main components of scaffold proteins in postsynaptic density (PSD), has been addressed as a candidate gene in autism spectrum disorders. To elucidate the disturbance of synaptic balance arising from Dlgap2 loss-of-function in vivo, we thus generated Dlgap2-/-mice to investigate their phenotypes of synaptic function and social behaviors.
Methods:
The creation of Dlgap2-/-mice was facilitated by the recombineering-based method, Cre-loxP system and serial backcross.
Reversal learning in a water T-maze was used to determine repetitive behaviors. The three-chamber approach task, resident-intruder test and tube task were performed to characterize the social behaviors of mutant mice.
Cortical synaptosomal fraction, Golgi-Cox staining, whole-cell patch electrophysiology and transmission electron microscopy were all applied to investigate the function and structure of synapses in the orbitofrontal cortex (OFC) of Dlgap2-/-mice.
Results:
Dlgap2-/-mice displayed exacerbated aggressive behaviors in the resident-intruder task, and elevated social dominance in the tube test. In addition, Dlgap2-/-mice exhibited a clear reduction of receptors and scaffold proteins in cortical synapses.
Dlgap2-/-mice also demonstrated lower spine density, decreased peak amplitude of miniature excitatory postsynaptic current and ultra-structural deficits of PSD in the OFC.
Conclusions:
Our findings clearly demonstrate that Dlgap2 plays a vital role in social behaviors and proper synaptic functions of the OFC. Moreover, these results may provide valuable insights into the neuropathology of autism.
Author: Li-Feng Jiang-XieHsiao-Mei LiaoChia-Hsiang ChenYuh-Tarng ChenShih-Yin HoDai-Hua LuLi-Jen LeeHorng-Huei LiouWen-Mei FuSusan Shur-Fen Gau
Credits/Source: Molecular Autism 2014, 5:32
Published on: 2014-05-01
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