An anatomically distinct dopaminergic cell population of the zona incerta as evidence for the human A13 nucleus

Abstract

The zona incerta (ZI) is a functionally and molecularly diverse deep brain region increasingly recognized as an integrative hub. The rodent ZI contains the dopaminergic A13 nucleus, with studies supporting a central role in modulating sensorimotor integration, nociception, and confers resilience in models of neurodegeneration; however, to date, no clear human homologue has been identified. Here, we identified a tyrosine hydroxylase-positive subregion in the human ZI consistent with the A13, and refined its borders using ex vivo MRI and histology. We translate these findings to in vivo MRI, demonstrating the A13 is distinguishable from surrounding regions by elevated T1 and T2* values. We further revealed a principal rostral-caudal axis of molecular and structural connectivity variation in the ZI, and identified the A13 as a localized molecular specialization. Altogether, we report a distinct ZI subregion corresponding to the A13 nucleus, providing an anatomical foundation for further mechanistic and translational investigation.