Stress effects on the adult prefrontal cortex

Dysregulation of the prefrontal inhibitory GABAergic system causes pathological changes to emotional behaviors. Parvalbumin cells are a subtype of interneuron that provides strong, fast-spiking inhibitory control in neural circuits. I contributed to the finding that chronic stress increases parvalbumin protein expression in the prefrontal cortex of female mice, which correlates with increased anxiety-like behavior. I then discovered that chemogenetic excitation of prefrontal parvalbumin cells replicates the behavioral effects of chronic stress, namely increased anxiety-like behavior in females. This work led to the hypothesis that prefrontal excitatory/inhibitory balance is disrupted by chronic stress in mice and in human cases of emotional disorders like anxiety and depression. Specifically, these conditions involve over-inhibition in the prefrontal cortex and therapeutic interventions may require lifting inhibition to restore a balance between inhibition and excitation.