Transcriptomic diversity of amygdalar subdivisions across humans and nonhuman primates

The amygdaloid complex mediates learning, memory, and emotions. Understanding the cellular and anatomical features that specialize the amygdala in primates versus other vertebrates first necessitates a systematic, anatomically-resolved molecular analysis of constituent cell populations. We analyzed tissue dissections of five nuclear subdivisions of the primate amygdala with single-nucleus RNA sequencing in macaques, baboons, and humans to examine gene expression profiles for excitatory and inhibitory neurons within and across nuclear subdivisions and confirm our results with single-molecule FISH analysis. We identified distinct subtypes of FOXP2+ interneurons in the intercalated cell masses and protein-kinase C- interneurons in the central nucleus. We also establish that glutamatergic, pyramidal-like neurons are transcriptionally specialized within the basal, lateral, or accessory basal nuclei. Understanding the molecular heterogeneity of anatomically-resolved amygdalar neuron types provides a cellular framework for improving existing models of how amygdalar neural circuits contribute to cognition and mental health in humans by using nonhuman primates as a translational bridge. Overall design: We obtained tissue blocks of postmortem human brain containing the amygdala from 5 human adult brain donors, 5 adult rhesus macaques, and 2 olive baboons. The whole basolateral complex was sampled indiscriminately in humans, whereas precise punches of either the lateral (LA), basal (BA), accessory basal (aBA), or central nucleus (CeA) were taken in nonhuman primates. We used the 10x Genomics 3' Single Cell Gene Expression platforms to generate single-nucleus RNA-seq data of the primate amygdala across all three species.