Investigating the Role of Adult-Generated Hippocampal Neurons in Early Life Adversity-Induced Changes in Defensive Behavior

Abstract

Adverse experiences early in life are known to be associated with an increased risk of developing anxiety and other mood disorders later in adulthood. To investigate how early life adversity (ELA) affects the brain in humans, researchers often turn to rodent models. Previous studies subjected rodents to ELA and found that ELA led to increases in defensive behavior and also a decrease in adult neurogenesis in the dentate gyrus (DG) of the hippocampus. However, there is still a lack of research on whether adult-born neurons play a modulating role in defensive behaviors when exposed to ELA. To answer the question, the present study subjected transgenic GFAP-TK mice and their wildtype littermates (CD1) to maternal separation with early weaning (MSEW) or non-handled control conditions during development. The two subgroups were then treated with an antiviral drug, valganciclovir (VGCV), in adulthood to ablate adult neurogenesis in the DG of the TK mice. Both CD1 and TK mice were then tested on the elevated plus maze (EPM) paradigm to determine if adult-generated neurons are necessary for the previously reported increases in the defensive behavior of ELA-subjected mice. Contrary to previous studies, we found that MSEW surprisingly did not affect defensive behavior, but the ablation of adult neurogenesis led to a significant decrease in defensive behavior in MSEW TK mice. These results suggest that MSEW may lead to changes in the functionality of adult-born neurons to induce a decrease in defensive behavior. It is possible that strain differences in mice impact the behavioral effects of ELA and lead to CD1 mice exhibiting a comparatively resilient phenotype in response to stress. Future work is needed to explore the specific mechanisms through which ELA may modulate adult neurogenesis to induce changes in defensive behaviors.