Rho Guanine Nucleotide Exchange Factor 4 (Arhgef4) Deficiency Enhances Spatial and Object Recognition Memory

Abstract

Guanine nucleotide exchange factors (GEFs) play multiple functional roles in neurons. In a previous study, we reported that <i>Arhgef4</i> (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 <i>Arhgef4</i> in behavior has not been examined. We performed comprehensive behavioral tests in knockout (KO) mice to investigate of the effects of <i>Arhgef4</i> deficiency. We found that the expressed PSD-95 particle size was significantly increased in hippocampal neuronal cultures from <i>Arhgef4</i> KO mice, which is consistent with the previous <i>in vitro</i> findings. <i>Arhgef4</i> 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 <i>Arhgef4</i> KO mice. Taken together, these data confirm the role of <i>Arhgef4</i> as a negative synaptic regulator at the behavioral level.