Receptor architecture shapes the regional organization of the macaque cingulate cortex

Abstract The cingulate cortex plays a central role in emotion, motivation, decision-making and motor control, yet its internal organization in the macaque brain remains debated. In the present study, we examined the cyto- and receptor architectonic organization of the macaque cingulate cortex and provide a 3D parcellation of the identified areas in both surface and volumetric representations. Multivariate receptor analyses consistently separated areas of the anterior cingulate cortex (ACC) and anterior midcingulate cortex (aMCC) from those of the posterior midcingulate cortex (pMCC) and posterior cingulate cortex (PCC), supporting the definition of four principal cingulate regions in the macaque brain. These regions are characterized by distinct receptor balances: the ACC is enriched with glutamatergic and monoaminergic receptors; the aMCC exhibits high densities of modulatory receptors; the pMCC is characterized by overall lowest receptor densities; and the PCC displays intermediate receptor densities with relatively higher GABA A and M 3 receptors. Within the ACC, receptor architecture revealed differentiation of subgenual, gyral and sulcal portions, while the PCC contained subdivisions corresponding to dorsal and ventral PCC. Cytoarchitectonic and receptor analyses further demonstrated that cortex along the dorsal bank of the cingulate sulcus (cgs) contains distinct cingulate areas extending from the sulcal fundus onto the dorsal wall, indicating that it forms part of the cingulate cortex rather than the frontal cortex or a transitional zone between those regions. Together, these findings provide a comprehensive anatomical and neurochemical framework for the macaque cingulate cortex and address the long-standing controversy regarding the dorsal bank of the cgs.