Organizational Principles of the Primate Cerebral Cortex at the Single-Cell Level

The primate cerebral cortex, the major organ for cognition, consists of an immense number of neurons. However, the organizational principles governing these neurons remain unclear. By accessing the single-cell spatial transcriptome of over 25 million neuron cells across the entire macaque cortex, it is discovered that the distribution of neurons within cortical layers is highly non-random. Strikingly, over three-quarters of these neurons are located in distinct neuronal clusters. Within these clusters, different cell types tend to collaborate rather than function independently. Typically, excitatory neuron clusters mainly consist of excitatory-excitatory combinations, while inhibitory clusters primarily contain excitatory-inhibitory combinations. Both cluster types have roughly equal numbers of neurons in each layer. Importantly, most excitatory and inhibitory neuron clusters form spatial partnerships, indicating a balanced local neuronal network and correlating with specific functional regions. These organizational principles are conserved across mouse cortical regions. These findings suggest that different brain regions of the cortex may exhibit similar mechanisms at the neuronal population level.