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Short Communication

Exp Neurobiol 2020; 29(5): 334-343

Published online October 31, 2020

© The Korean Society for Brain and Neural Sciences

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

Ki-Seo Yoo1, Kina Lee1, Yong-Seok Lee2, Won-Jong Oh3 and Hyong Kyu Kim1*

1Department of Medicine and Microbiology, Graduate Program in Neuroscience, College of Medicine, Chungbuk National University, Cheongju 28644, 2Department of Physiology, Department of Biomedical Science, Seoul National University College of Medicine, Seoul 03080, 3Neurovascular Unit Research Group, Korea Brain Research Institute, Daegu 41062, Korea

Correspondence to: *To whom correspondence should be addressed.
TEL: 82-43-261-2867, FAX: 82-43-272-1603

Received: October 9, 2020; Revised: October 12, 2020; Accepted: October 12, 2020

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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.

Graphical Abstract

Keywords: Arhgef4, PSD-95, Spatial memory, Recognition