Cell Atlas and Novel Signal Processing Strategy in Primate Insular Cortex [scRNA-seq]

The anterior insular cortex (AIC) is a critical hub integrating exteroceptive and interoceptive information into high-order cognition, yet its neural basis remains incompletely understood. Here, by combining whole-cell-based single-cell transcriptomics with Patch-seq recordings, we resolved and characterized 78 detailed cell types in the macaque AIC, revealing the diversity and specialization of this region in cell type, connectivity profile, signal-processing strategy, and metabolic characteristics. Among these, we identified two transcriptomically and morphoelectrically defined von Economo neuron (VEN) subtypes, DSG2-expressing VEN-L and POC5-expressing VEN-S, transcriptomically relating to extratelencephalic and corticothalamic projection neurons, respectively. We also uncovered a previously underappreciated signal-processing strategy in VENs, whereby the geometry of the dendrite-originating axon initial segment (AIS) reshapes action potential dynamics and enhances somatic responsiveness to deep-layer synaptic inputs. Together, this multimodal atlas establishes a molecular and functional framework for investigating the circuit principles underlying deep-layer projection neurons in the primate AIC. Overall design: Here we employed a massively parallel 10X genomics single cell RNA-sequencing (scRNA-seq) analysis of the AIC to derive a molecular classification and then related each molecularly distinct cell type to well-established AIC cell types via Patch-seq.