Prefrontal cortex is necessary for long-term social recognition memory in mice

The prefrontal cortex (PFC) plays critical roles in social cognition and emotional regulation in humans and rodents; however, its involvement in social recognition memory in mice remains unclear. Here, we examined the roles of the PFC in short-term and long-term social recognition memory, social motivation, and anxiety-related behavior in C57BL/6J male mice. Sham control and PFC-lesioned mice underwent four different behavioral tests. In the social recognition test, composed of three daily trials over 3 consecutive days, the control mice spent less time investigating the juvenile stimulus mouse both within each day and across days. By contrast, while social investigation behavior in PFC-lesioned mice decreased across the three trials within each day, it did not decrease over the 3-day testing period. These results indicate that the PFC has an important role in long-term, but not short-term, social recognition memory. The control and PFC-lesioned mice exhibited similar social motivation in the three-chamber test - both groups preferred the juvenile mouse to the empty cylinder and did not prefer the adult mouse. In addition, the PFC lesion had no impact on anxiety-related behavior or general activity in the light-dark transition test or the open field test. Our findings demonstrate that the PFC is essential for long-term social recognition memory and that it plays a critical role in higher-order social cognition.