The Activating Transcription Factor 3 () Homozygous Knockout Mice Exhibit Enhanced Conditioned Fear and Down Regulation of Hippocampal .

The genetic and molecular basis underlying fear memory formation is a key theme in anxiety disorder research. Because activating transcription factor 3 () is induced under stress conditions and is highly expressed in the hippocampus, we hypothesize that plays a role in fear memory formation. We used fear conditioning and various other paradigms to test knockout mice and study the role of in processing fear memory. The results demonstrated that the lack of specifically enhanced the expression of fear memory, which was indicated by a higher incidence of the freeze response after fear conditioning, whereas the occurrence of spatial memory including Morris Water Maze and radial arm maze remained unchanged. The enhanced freezing behavior and normal spatial memory of the knockout mice resembles the fear response and numbing symptoms often exhibited by patients affected with posttraumatic stress disorder. Additionally, we determined that after fear conditioning, dendritic spine density was increased, and expression of , the gene encoding a severing protein for actin polymerization, was down-regulated in the bilateral hippocampi of the knockout mice. Taken together, our results suggest that may suppress fear memory formation in mice directly or indirectly through mechanisms involving modulation of actin polymerization.