Dexter_2026_Nat.Commun__

The prefrontal cortex (PFC) is known to mediate working memory processes, although how individual circuit elements within PFC support working memory is much less well understood. Parvalbumin-expressing neurons (PVNs) are inhibitory cells involved in coordinating local communication and facilitate the emergence of high frequency gamma oscillations. PVNs are shown to support various PFC-dependent cognitive functions in rodents, though reports of their involvement in working memory have yielded conflicting results. Here, we implemented in vivo fiber photometry and optogenetics to record and manipulate prefrontal PVN activity during a touchscreen-based test of working memory in mice. We found that PVN involvement is highly dependent on task demands, making a necessary contribution through heightened activity only during high-demand conditions. These findings suggest that previous contradictory findings regarding the role of prefrontal PVNs in working memory may be due to differences in the degree to which the working memory paradigms used taxed cognitive load.