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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.

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