Prefrontal parvalbumin neurons mediate working memory in a task demand-dependent manner

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. There has been conflicting evidence on the role of parvalbumin expressing neurons (PVNs) in the prefrontal cortex in working memory. Here, the authors show that prefrontal PVN activity scales with task demands during working memory, that optimal activity is critical for performance under conditions of increased delay length and interference, and that gamma-frequency stimulation of PVNs improves working memory performance.