Parvalbumin-expressing GABAergic interneurons and perineuronal nets in the prelimbic and orbitofrontal cortices in association with basal anxiety-like behaviors in adult mice

Parvalbumin-expressing (PV⁺) GABAergic interneurons are the principal inhibitory interneurons in the cortex, and a decrease in their number or PV protein expression is associated with changes in brain function. PV⁺ neurons are surrounded by the perineuronal net (PNN), a reticular extracellular matrix structure surrounding the soma and proximal dendrites. Although the prefrontal cortex is critically involved in anxiety-like behavior, it is not known how cortical PV⁺ neurons enwrapped with PNN contribute to basal anxiety behavior. To address the issue, we employed Wisteria floribunda agglutinin (WFA) to label the PNN and measured the densities and PV immunofluorescence of PV⁺ neurons, including those enwrapped with PNN (i.e., PV⁺WFA⁺ neurons) in the orbitofrontal (OFC) and prelimbic cortices of mice whose basal anxiety levels had been assessed in the open field test. We found that these densities, but not PV expression according to immunofluorescence intensity, were positively correlated with the percentage of time spent and the distance traveled in the center of an open field. Thus, these data demonstrate that the densities of OFC PV⁺ and PV⁺WFA⁺ neurons are significantly inversely correlated with basal anxiety levels of adult mice measured in the open field test and may represent a target for future anxiolytic therapeutics.