Guanine nucleotide exchange factors (GEFs) play multiple functional roles in neurons. In a previous study, we reported that Arhgef4 (Rho guanine nucleotide exchange factor 4) functioned as a negative regulator of the excitatory synaptic function by sequestering postsynaptic density protein 95 (PSD-95). However, the role of Arhgef4 in behavior has not been examined. We performed comprehensive behavioral tests in knockout (KO) mice to investigate of the effects of Arhgef4 deficiency. We found that the expressed PSD-95 particle size was significantly increased in hippocampal neuronal cultures from Arhgef4 KO mice, which is consistent with the previous in vitro findings. Arhgef4 KO mice exhibited general motor activity and anxiety-like behavior comparable to those of the wild type littermates. However, spatial memory and object recognition memory were significantly enhanced in the Arhgef4 KO mice. Taken together, these data confirm the role of Arhgef4 as a negative synaptic regulator at the behavioral level.

中文翻译：

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Rho鸟嘌呤核苷酸交换因子4（Arhgef4）缺乏症可增强空间和物体识别记忆。

鸟嘌呤核苷酸交换因子（GEF）在神经元中发挥多种功能。在先前的研究中，我们报道了Arhgef4（Rho鸟嘌呤核苷酸交换因子4）通过隔离突触后密度蛋白95（PSD-95）而充当兴奋性突触功能的负调节剂。但是，尚未检查Arhgef4在行为中的作用。我们在基因敲除（KO）小鼠中进行了全面的行为测试，以研究Arhgef4缺乏症的影响。我们发现从Arhgef4 KO小鼠海马神经元培养物中表达的PSD-95粒径显着增加，这与以前的体外发现一致。Arhgef4KO小鼠表现出与野生同窝小鼠相当的一般运动活动和类似焦虑的行为。但是，在Arhgef4 KO小鼠中，空间记忆和物体识别记忆显着增强。综上所述，这些数据在行为水平上证实了Arhgef4作为负突触调节剂的作用。