GABAergic interneurons in local circuits of primate prefrontal cortex.

Cortical GABAergic interneurons exhibit remarkable diversity of morphological, electrophysiological and molecular features, which underlies their specialized roles in circuit functions. Molecular characteristics have proven to be a reasonable starting point in the past for classification, grouping them into parvalbumin (PV), somatostatin (SST), vasoactive intestinal polypeptide (VIP) and "others" (e.g. LAMP5). While Patch-seq studies provide valuable insight into human cortical interneurons, similar results from non-human primates are lagging behind. This is problematic because the studying of cell types, circuits and behavior in a detailed experimental fashion is still out of reach in the human. Therefore, using the extensive knowledge from the mouse model as a ground truth, we explore how recent studies of GABAergic interneurons in marmoset and macaque add to our understanding of the expanding variety of cell types and subtypes in primates compared to rodents. Our knowledge of which interneuron participates in which basic circuit motif, like feedforward, feedback, local and lateral inhibition as well as disinhibition is still very limited. However, the more diverse molecular, physiological and morphological features of primate interneurons should allow a broader range of circuit motifs, increasing the computational power of prefrontal cortical circuits. This increased complexity likely supports advanced cognitive functions such as working memory but may also heighten vulnerability to neuropsychiatric disorders. We argue that primate-specific interneuron diversity is not merely a quantitative expansion but a functional innovation, with profound implications for understanding cognition and disease.