Comparative molecular mapping reveals molecular gradients and spatially organized populations in the subthalamic and para-subthalamic regions

HTR2C is enriched in the ventral subthalamic nucleus (STN) in macaque and human tissue but is broadly distributed across the mouse STN, with an opposite gradient to PVALB.

• Why it matters: Molecular organization of the STN and its relationship to the adjacent para-subthalamic nucleus (pSTN) is incompletely defined, limiting precise anatomical and molecular targeting for Parkinson disease DBS.
• What they did: The authors performed comparative molecular mapping of STN and pSTN in mouse and macaque, complemented by a human tissue sample, 3D imaging, and publicly available spatial transcriptomic datasets. They identified rostrocaudal and dorsolateral molecular gradients and additional mediolateral Nts gradients in mouse.
• The result: TAC1 characterized the canonical pSTN in both species but also an extended population reaching dorsally along the medial STN, overlapping the region traversed by tyrosine hydroxylase-positive medial forebrain bundle fibers. These results refine a spatially heterogeneous, multiaxial molecular framework for the subthalamic region.