Early growth response 2 regulates mouse cooperative behavior

Abstract

Social cooperation is essential to animals’ physical health and psychological state. However, the underlying molecular and neurobiological mechanisms remain poorly understood. Here, we established a novel model for systematically evaluating the cooperative behavior of mice for the task of water reward. Using this paradigm, we characterized cooperative deficits in isolated juvenile mice and the corrective effect of resocialization. Mechanistically, we found that the transcription factor early growth response 2 (Egr2)-dependent myelin maturation in the medial prefrontal cortex is necessary for the development of mice’s cooperative behavior. Additionally, corticosterone levels in the serum and medial prefrontal cortex were elevated in the isolated mice, potentially contributing to Egr2 expression reduction. This work suggests targeting Egr2 could be targeted for preventing and treating social isolation-related neuropsychiatric disorders in the future.