Prelimbic Cortex Activity Predicts Anxiety‐Like Behavior in the Elevated Plus Maze

ABSTRACT The medial prefrontal cortex plays a critical role in emotional regulation, and its dysregulation is linked to anxiety disorders. In particular, the prelimbic cortex of the medial prefrontal cortex is thought to modulate anxiety‐related behaviors, though its precise role remains debated. Here, we used endoscopic in vivo calcium imaging to assess prelimbic neuronal activity in male and female Sprague–Dawley rats performing in the Elevated Plus Maze, a widely used task to measure anxiety‐like behavior. We found that animals that spent less time in the open arms exhibited higher prelimbic activity in the open arms, suggesting that heightened prelimbic activity may reflect greater anxiety or increased avoidance behavior. These results suggest that the prelimbic cortex may play a role in regulating the emotional response to anxiety‐provoking situations, potentially influencing the tolerance for exposure to threatening environments.