Prefrontal cortex neurons in adult rats exposed to early life stress fail to appropriately signal the consequences of motivated actions

Abstract

Early life stress (ELS) can set the stage for susceptibility to cognitive and emotional dysfunction in adulthood by disrupting typical neural development. The prefrontal cortex (PFC) continues to mature during early life, making this region particularly vulnerable to disruption for animals who experience ELS. Despite this, the effects of ELS experience on in vivo PFC function in awake and behaving adult animals are currently poorly understood. To assess this, we employed an instrumental conflict task to assess how hungry adult rats, either ELS (wet bedding) or unstressed Controls, were able to flexibly alter their motivation for food reward seeking (lever presses) in situations that were either threatening or safe. During this task, in vivo electrophysiological recordings (both single unit and local field potentials [LFPs]) were made in the rats’ ventral-medial PFC (vmPFC). We found that ELS rats were less motivated to lever press for rewards than Controls in the threat situations during repeated extinction sessions. In recordings taken during this suppression task, Control vmPFC neurons displayed reliable differences between motivated actions, such as between rewarded and unrewarded presses, but ELS neurons failed to differentiate these action-outcome differences. We also found differences in task-related LFP activity between groups; in particular, prior ELS experience appears to induce abnormal changes in low-frequency oscillations during shock-associated threat stimuli prior to presses, as well as diminished higher-frequency oscillations following rewarded presses. Collectively, we demonstrate that ELS experience produces persistent impairment in motivational regulation that is associated with significant changes in in vivo PFC signals. Specifically, ELS-experienced adults fail to appropriately update motivated action strategies under threat conditions, and likewise fail to appropriately monitor and update action/outcome relationships in motivated behavior. These ELS-related changes may therefore lay the foundation for heightened susceptibility to mental-health disorders in adults such as substance abuse and post-traumatic stress disorder.