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Cross-species consensus atlas of the primate basal ganglia
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Cross-species consensus atlas of the primate basal ganglia

Nelson J. Johansen, Yuanyuan Fu, Matthew Schmitz +97 more
December 2025
 ·
bioRxiv
 ·
DOI 
10.64898/2025.12.15.694496
94
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It ranks in the top 1% of preprints assessed in Neuroscience this quarter.
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Why this is interesting

By establishing the first cross-species multiomic atlas of the primate basal ganglia, this work resolves a unified cell-type taxonomy that anchors psychiatric disease risk to specific neuron types and enables sequence-driven, cell-type-targeted therapeutic strategies.

QED claims analysis

Summary

A multiomic consensus atlas of 1.8 million nuclei across human, macaque, and marmoset basal ganglia defines 61 conserved cell types and reveals that dorsal-ventral spatial patterning is more evolutionarily constrained than direct-indirect pathway or striosome-matrix molecular identity, while conserved transcription factor motif grammars specify cell type-specific enhancer activity and psychiatric disease risk is preferentially enriched in ventral striatal medium spiny neuron populations.

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Main Claim 1 –

Consensus primate basal ganglia taxonomy defines 61 homologous cell types

Supporting evidence

  • Spatial and Patch-seq data anchor taxonomy to anatomy and function
Main Claim 2 –

MSN dorsoventral patterning is more conserved than pathway identity

Supporting evidence

  • Homology mapping reveals conserved STRd D2 StrioMat Hybrid MSNs
Main Claim 3 –

Conserved TF motif grammars specify basal ganglia enhancers across mammals

Supporting evidence

  • Deep sequence models predict enhancer activity and guide viral targeting
Main Claim 4 –

Psychiatric GWAS risk preferentially enriches in ventral striatal MSNs

Abstract

The basal ganglia (BG) are conserved brain regions essential for motor control, learning, emotion, and cognition, and are implicated in neurological and psychiatric disease. Yet a unified cross-species taxonomy of BG cell types is lacking, limiting translation of BG circuit mechanisms, interpretation of human genetic risk, and development of cell type-targeted tools. We present a multiomic consensus atlas of 1.8 million nuclei from human, macaque, and marmoset spanning eight BG structures. Integrating cross-species gene expression, open chromatin, and spatial profiling enables definition of conserved and divergent cell types. Alignment to existing mouse and human atlases identifies 61 homologous cell types conserved over 80 million years. We identify a STRd D2 StrioMat Hybrid medium spiny neuron (MSN) type with molecular, electrophysiological, and morphological features that clarify hybrid MSN identities. Comparative cis-regulatory analysis reveals conserved sequence grammars that encode cell identity and inform viral targeting strategies, providing a foundational resource for BG evolution, function, and disease.

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