Multimodal Nature of the Single-cell Primate Brain Atlas: Morphology, Transcriptome, Electrophysiology, and Connectivity.

Primates exhibit complex brain structures that augment cognitive function. The neocortex fulfills high-cognitive functions through billions of connected neurons. These neurons have distinct transcriptomic, morphological, and electrophysiological properties, and their connectivity principles vary. These features endow the primate brain atlas with a multimodal nature. The recent integration of next-generation sequencing with modified patch-clamp techniques is revolutionizing the way to census the primate neocortex, enabling a multimodal neuronal atlas to be established in great detail: (1) single-cell/single-nucleus RNA-seq technology establishes high-throughput transcriptomic references, covering all major transcriptomic cell types; (2) patch-seq links the morphological and electrophysiological features to the transcriptomic reference; (3) multicell patch-clamp delineates the principles of local connectivity. Here, we review the applications of these technologies in the primate neocortex and discuss the current advances and tentative gaps for a comprehensive understanding of the primate neocortex.