Molecular and cellular changes underlying evolutionary specializations of primate dorsolateral prefrontal cortex

The granular dorsolateral prefrontal cortex (dlPFC) is an evolutionary specialization of primates that is centrally involved in cognition. Here, we assessed over 600,000 single-nucleus transcriptomes from human, chimpanzee, macaque, and marmoset dlPFC. While major subclasses of transcriptomically-defined cell subtypes are conserved, we detected several subtypes only in some species and substantial species-specific molecular differences across homologous neuronal, glial and non-neural subtypes. The latter are exemplified by human-specific switching between translation of the neuropeptide somatostatin (SST) and tyrosine hydroxylase (TH), the rate-limiting enzyme in dopamine production, in certain interneurons, and also by expression of the neuropsychiatric risk gene FOXP2, which is human-specific in microglia and primate-specific in layer-4 granular neurons. We generated a comprehensive transcriptomic and cellular survey of dlPFC evolution in anthropoid primates. Overall design: Gene expression profiling of mouse neocortices after being electroporated with GFP or human/mouse FOXP2