**14. Parvalbumin interneurons and the prefrontal cortex**

The prefrontal cortex (PFC) is the neuroanatomical hub for executive functions such as working memory, which can be metaphorically thought of as the brain's blackboard [21, 71]. Incoming stimuli are transiently stored, manipulated, updated, and guide goal‐directed behavior [72]. Working memory is dependent on prefrontal circuitry involving the unique balance between pyramidal Delay excitatory neurotransmission and GABAergic interneu‐ ronal inhibition [57, 62, 71]. Excitatory Delay cells become activated upon presentation of a salient cue and sustain neuronal activity throughout a delay period, essentially 'remember‐ ing' the cue, and allowing an appropriate response. For instance, **Figure 8** represents an

**Figure 8.** Single unit electrophysiological activity of a Delay cell in the primate DLPFC during a working memory task. The onset of Delay cell activity is triggered by the presence of relevant stimuli, or a cue. In the absence of a visual cue, Delay cells persistently fire during the delay period and allow for the generation of a goal‐directed response (e.g., saccade). The sustained neuronal firing during the delay period is hypothesized to be the neural correlate of working memory and depends on both excitatory pyramidal activity as well as fast‐spiking GABAergic interneurons in the DLPFC [21, 71, 73, 74] (Modified from Monaco et al. [21]).

example of single unit prefrontal Delay cell activity in the primate dorsolateral prefrontal cortex (DLPFC) during an oculomotor delayed‐response task. In this working memory task, subjects are trained to fix their gaze at the center. A single cue is presented somewhere in the 360° perimeter, followed by a brief delay period in which the cue is absent. After the delay period, an appropriate response would be an eye saccade in the direction that the cue was first presented.

Working memory, the sustained neuronal activity that occurs during the delay, is not only dependent on prefrontal pyramidal cells, but also fast‐spiking GABAergic interneurons [57, 62, 71]. Pharmacological evidence supports the importance of fast‐spiking interneu‐ rons in the DLPFC for working memory function. Administration of a GABAAR antagonist, bicuculline, lead to impaired mnemonic tuning during an oculomotor delayed‐response task. Therefore, working memory, particularly sustained neuronal activity during the delay period, depends on GABAA receptors. Furthermore, GABAergic hypofunctioning in the DLPFC partly contributes to working memory deficits [62, 75]. GABAergic neuro‐ nal activity and its role in working memory function are also connected to gamma oscilla‐ tions. Gamma oscillations, which fall in the band range between 30 and 60 Hz, are required for working memory function. A research study conducted in 2003 reported that gamma band oscillations increased proportionally with working memory load [57, 62, 76]. More specifically, fast‐spiking PV interneurons are a crucial input for gamma rhythm genera‐ tion. Inhibition of PV interneurons attenuates gamma oscillations, whereas driving PV neuronal activity initiates gamma‐frequency rhythms [62]. Excitatory pyramidal output in the prefrontal cortex is modulated by inhibitory gamma oscillations, largely driven my PV‐ interneurons, essentially fine‐tuning the circuit and allowing for proper working memory function. Conclusively, PFC‐dependent working memory involves a symbiotic balance between excitatory pyramidal output and fast inhibitory activity of PV‐interneurons, which shapes and fine‐tunes the circuit.
