Prefrontal cortex interneurons and their contributions to attention, working memory, and adaptive behavior

Inhibitory interneurons play central roles in regulating the input and output of cortical circuits, which in prefrontal cortices (PFC) subserve attention control, working memory and adaptive behavior. Understanding how interneurons support these higher order cognitive functions is a key question in a growing number of studies. Here, we delineate recent progress by surveying molecular, functional and computational motifs of interneurons in the prefrontal cortex of nonhuman primates and rodents. Among multiple transcriptomic and molecular subtypes of neurons several electrophysiologically identified 'eType' interneurons are recruited during attention, learning, and working memory tasks. In nonhuman primate PFC, eType neurons with an inhibitory effect on the local circuit encode behaviorally relevant cues, unexpected outcomes, and tune working memory representations. These response profiles are consistent with the functional specializations proposed for PV+ , SST+ and VIP+ interneurons in rodents, which are recruited during attention and memory-guided tasks. We survey how these functional studies of interneuron types are supported by newly developed molecular and analytical tools and guided by computational studies that suggest unique circuit motifs for distinct types of interneurons to flexibly route synaptic inputs, compute prediction errors, and facilitate information retention in working memory.