Prefrontal parvalbumin cells are sensitive to stress and mediate anxiety-related behaviors in female mice

Reduced activity of the prefrontal cortex (PFC) is seen in mood disorders including depression and anxiety. The mechanisms of this hypofrontality remain unclear. Because of their specific physiological properties, parvalbumin-expressing (PV(+)) inhibitory interneurons contribute to the overall activity of the PFC. Our recent work using a chronic stress mouse model showed that stress-induced increases in prefrontal PV expression correlates with increased anxiety-like behaviors in female mice. Our goal is now to provide a causal relationship between changes in prefrontal PV(+) cells and changes in emotional behaviors in mice. We first show that, in addition to increasing overall level of PV expression, chronic stress increases the activity of prefrontal PV(+) cells. We then used a chemogenetic approach to mimic the effects of chronic stress and specifically increase the activity of prefrontal PV(+) cells. We observed that chemogenetic activation of PV(+) cells caused an overall reduction in prefrontal activity, and that chronic activation of PV(+) cells lead to increased anxiety-related behaviors in female mice only. These results demonstrate that activity of prefrontal PV(+) cells could represent a novel sex-specific modulator of anxiety-related behaviors, potentially through changes in overall prefrontal activity. The findings also support the idea that prefrontal PV(+) cells are worth further investigation to better understand mood disorders that are more prevalent in female populations.