Interneuron diversity in the human dorsal striatum

Area of Science:

• Neuroscience
• Genomics
• Cell Biology

Background:

• Understanding the basal ganglia circuit is crucial for neurological and psychiatric disease research.
• Striatal interneurons play a vital role in basal ganglia function.
• Existing classifications of striatal interneurons require further refinement.

Purpose of the Study:

• To comprehensively characterize the diversity and transcriptional landscape of human striatal interneurons.
• To develop a standardized taxonomy of striatal interneuron populations.
• To investigate the spatial distribution and abundance of these interneurons in the human dorsal striatum.

Main Methods:

• Single-nucleus RNA sequencing (snRNA-seq) of postmortem human caudate nucleus and putamen.
• Spatial transcriptomics to map interneuron populations within the striatum.
• Quantitative fluorescence in situ hybridization (FISH) for validation.

Main Results:

• A novel taxonomy of striatal interneurons with eight main classes and fourteen subclasses was established.
• Detailed transcriptomic identities and spatial expression profiles for each population were provided.
• Correspondence with existing classifications and differences between caudate nucleus and putamen were delineated.
• Abundant interneuron populations, including PTHLH and TAC3 types, showed parallels with mouse counterparts.

Conclusions:

• The proposed taxonomy offers a harmonized framework for human striatal interneuron classification.
• This research provides critical insights into the cellular architecture of the human dorsal striatum.
• The findings support the generalizability of the taxonomy and its integration with other datasets, advancing basal ganglia research.