Comprehensive 3D mapping reveals distinct spatial gradients of SST, PV, and TH interneurons across the mouse caudoputamen

Abstract

In addition to spatially organized excitatory forebrain inputs along its mediolateral, dorsoventral, and anteroposterior axes, the striatum relies on cellular diversity to subserve its myriad processing functions. Distinct striatal GABAergic interneuron subtypes, including somatostatin (SST), parvalbumin (PV), and tyrosine hydroxylase (TH) interneurons likely subserve complementary computational roles. However, a detailed understanding of how these microcircuit components are distributed across striatal territories remains lacking. To address this gap, we generated a comprehensive three-dimensional atlas of SST, PV, and TH interneurons across the mouse caudoputamen using genetic labeling, brain-wide imaging, and voxel-wise quantification. We found that SST and TH interneurons were relatively enriched in the ventral caudoputamen, whereas PV interneurons were enriched dorsally. In addition, PV and TH interneurons exhibited opposing anteroposterior distribution patterns, with PV interneurons enriched posteriorly and TH interneurons showing a marked decline in density towards the striatal tail. Consequently, while the three interneuron subtypes displayed comparable densities in the functionally defined lateral striatum and anterior ventromedial striatum, PV interneurons predominated in the dorsomedial striatum and tail of striatum. We did not observe major sex differences. Together, these findings reinforce the view that the striatum is not a monolithic structure: in addition to structured excitatory inputs, inhibitory microcircuits themselves are differentially distributed across striatal territories, providing region-specific constraints on circuit computation. By integrating interneuron organization into existing anatomical frameworks, this atlas provides a foundation for linking striatal anatomy to function across behavioral domains.