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

Sci Rep. 2019 Dec 24;9(1):19772. doi: 10.1038/s41598-019-56424-9.


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.

MeSH terms

  • Animals
  • Anxiety / metabolism*
  • Anxiety / pathology
  • Behavior, Animal*
  • Disease Models, Animal
  • Female
  • Gene Expression Regulation*
  • Interneurons / metabolism*
  • Interneurons / pathology
  • Male
  • Mice
  • Parvalbumins / biosynthesis*
  • Prefrontal Cortex / metabolism*
  • Prefrontal Cortex / pathology
  • Stress, Psychological / metabolism*
  • Stress, Psychological / pathology


  • Parvalbumins