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

<jats:title>Abstract</jats:title><jats:p>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<jats:sup>+</jats:sup>) 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<jats:sup>+</jats:sup> 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<jats:sup>+</jats:sup> cells. We then used a chemogenetic approach to mimic the effects of chronic stress and specifically increase the activity of prefrontal PV<jats:sup>+</jats:sup> cells. We observed that chemogenetic activation of PV<jats:sup>+</jats:sup> cells caused an overall reduction in prefrontal activity, and that chronic activation of PV<jats:sup>+</jats:sup> cells lead to increased anxiety-related behaviors in female mice only. These results demonstrate that activity of prefrontal PV<jats:sup>+</jats:sup> 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<jats:sup>+</jats:sup> cells are worth further investigation to better understand mood disorders that are more prevalent in female populations.</jats:p>