1. Diversity of interneurons in the dorsal striatum revealed by single-cell RNA sequencing and PatchSeq
- Author
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Nathan G. Skene, Ana B. Muñoz-Manchado, Jesper Ryge, Peter Lönnerberg, Bo Bekkouche, Kenneth D. Harris, Hermany Munguba, Sten Linnarsson, Jens Hjerling-Leffler, Amit Zeisel, and Carolina Bengtsson Gonzales
- Subjects
0301 basic medicine ,CALCIUM-BINDING PROTEIN ,EXPRESSING NEURONS ,fast-spiking neurons ,Interneuron ,striatum ,Striatum ,interneuron ,General Biochemistry, Genetics and Molecular Biology ,Article ,single-cell RNA sequencing ,cell classes ,03 medical and health sciences ,Mice ,0302 clinical medicine ,FAST-SPIKING INTERNEURONS ,BASAL GANGLIA ,Interneurons ,GABAERGIC INTERNEURONS ,Basal ganglia ,parvalbumin ,medicine ,Animals ,Humans ,PROJECTION NEURONS ,Pthlh ,Science & Technology ,biology ,K+ CHANNELS ,Sequence Analysis, RNA ,RAT NEOSTRIATUM ,RNA ,MOUSE STRIATUM ,Cell Biology ,electrophysiology ,Corpus Striatum ,Cortex (botany) ,Cell biology ,Electrophysiology ,030104 developmental biology ,medicine.anatomical_structure ,cortex ,nervous system ,biology.protein ,GABAergic ,Life Sciences & Biomedicine ,030217 neurology & neurosurgery ,Parvalbumin ,FEEDFORWARD INHIBITION - Abstract
Summary Striatal locally projecting neurons, or interneurons, act on nearby circuits and shape functional output to the rest of the basal ganglia. We performed single-cell RNA sequencing of striatal cells enriching for interneurons. We find seven discrete interneuron types, six of which are GABAergic. In addition to providing specific markers for the populations previously described, including those expressing Sst/Npy, Th, Npy without Sst, and Chat, we identify two small populations of cells expressing Cck with or without Vip. Surprisingly, the Pvalb-expressing cells do not constitute a discrete cluster but rather are part of a larger group of cells expressing Pthlh with a spatial gradient of Pvalb expression. Using PatchSeq, we show that Pthlh cells exhibit a continuum of electrophysiological properties correlated with expression of Pvalb. Furthermore, we find significant molecular differences that correlate with differences in electrophysiological properties between Pvalb-expressing cells of the striatum and those of the cortex., Graphical Abstract, Highlights • Single-cell RNA sequencing of striatal interneurons reveals seven main classes • Subclass-specific latent factor analysis reveals gradients of gene expression • Pvalb neurons are not a discrete class but belong to a class expressing Pthlh • Interneuron classes vary in their similarity to counterparts from cortex/hippocampus, Muñoz-Manchado et al. describe the molecular and electrophysiological diversity of interneurons from the striatum. They find that in contrast to many other brain regions, cells expressing the gene Pvalb are not a discrete class of cells. This affects the interpretation of studies on striatal networks and their function.
- Published
- 2018