Interneuron diversity in the human dorsal striatum

Leonardo D. Garma, Lisbeth Harder, Juan M. Barba-Reyes, Sergio Marco Salas, Mónica Díez-Salguero, Mats Nilsson, Alberto Serrano-Pozo, Bradley T. Hyman and Ana B. Muñoz-Manchado ()
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Leonardo D. Garma: Department of Medical Biochemistry and Biophysics
Lisbeth Harder: Department of Medical Biochemistry and Biophysics
Juan M. Barba-Reyes: Medicina Legal y Forense y Toxicología. Instituto de Investigación e Innovación Biomédica de Cádiz (INiBICA). University of Cádiz
Sergio Marco Salas: Stockholm University
Mónica Díez-Salguero: Medicina Legal y Forense y Toxicología. Instituto de Investigación e Innovación Biomédica de Cádiz (INiBICA). University of Cádiz
Mats Nilsson: Stockholm University
Alberto Serrano-Pozo: Neurology Department, Boston
Bradley T. Hyman: Neurology Department, Boston
Ana B. Muñoz-Manchado: Department of Medical Biochemistry and Biophysics

Nature Communications, 2024, vol. 15, issue 1, 1-19

Abstract: Abstract Deciphering the striatal interneuron diversity is key to understanding the basal ganglia circuit and to untangling the complex neurological and psychiatric diseases affecting this brain structure. We performed snRNA-seq and spatial transcriptomics of postmortem human caudate nucleus and putamen samples to elucidate the diversity and abundance of interneuron populations and their inherent transcriptional structure in the human dorsal striatum. We propose a comprehensive taxonomy of striatal interneurons with eight main classes and fourteen subclasses, providing their full transcriptomic identity and spatial expression profile as well as additional quantitative FISH validation for specific populations. We have also delineated the correspondence of our taxonomy with previous standardized classifications and shown the main transcriptomic and class abundance differences between caudate nucleus and putamen. Notably, based on key functional genes such as ion channels and synaptic receptors, we found matching known mouse interneuron populations for the most abundant populations, the recently described PTHLH and TAC3 interneurons. Finally, we were able to integrate other published datasets with ours, supporting the generalizability of this harmonized taxonomy.

Date: 2024
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DOI: 10.1038/s41467-024-50414-w

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