Diversity of Interneurons in the Dorsal Striatum Revealed by Single-Cell RNA Sequencing and PatchSeq

Abstract

SummaryStriatal 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.

Emerging links between cerebrovascular and neurodegenerative diseases—a special role for pericytes

“…Thus, more than 500 molecularly distinct classes of neurons and glial cells have been identified in the mouse brain [1,2], and information about the cellular composition of specific brain regions is increasing rapidly [2][3][4][5][6][7][8]. In addition, there is an even larger number of supporting glial cells, i.e., astrocytes and oligodendrocytes, the latter forming myelin sheets around neurons and making up a large part of the white matter in the brain.…”

“…While neurons and glial cells traditionally have been classified into sub-categories based on morphological and anatomical criteria or differences in neurotransmitter repertoire, a new and more fine-grained view of neurons and glial cell sub-types is now emerging as a result of recent transcriptomic analyses of the brain at the single-cell level. Thus, more than 500 molecularly distinct classes of neurons and glial cells have been identified in the mouse brain [1,2], and information about the cellular composition of specific brain regions is increasing rapidly [2][3][4][5][6][7][8]. Insights into the developmental trajectories for the different cell lineages-proceeding from immature progenitors to specialized cells -are generated by computational analyses of single-cell transcriptomes derived from different developmental stages [8][9][10].…”

Phenotypic variation within and across transcriptomic cell types in mouse motor cortex

“…For more than a century, neurons have been classified into types by their anatomical and physiological characteristics, and more recently by molecular markers (Harris and Shepherd, 2015;Tremblay et al, 2016;Kepecs and Fishell, 2014;Rudy et al, 2011). In the last years, development of high-throughput single-cell sequencing techniques allowed to identify dozens of neural types based on their transcriptional profiles (Tasic et al, 2016Zeisel et al, 2015Zeisel et al, , 2018, but linking the transcriptomically defined cell types to their phenotypes has remained a major challenge (Huang and Paul, 2019). At the same time, to understand the role that transcriptomic neural types play in cortical computations, it is necessary to know their anatomy, connectivity, and electrophysiology (Zeng and Sanes, 2017).…”

Nucleus Accumbens Fast-Spiking Interneurons Constrain Impulsive Action

“…Stereotaxic injection of Cre-dependent adeno-associated virus (AAV) labeled cells with electrophysiological characteristics of FSIs (Figure S1A-C), including a high maximum firing rate, narrow action potential half-width, and short-duration afterhyperpolarization (46). Most cells also expressed mRNA transcripts for parvalbumin (Pvalb) or parathyroid hormone like hormone (Pthlh), two markers of striatal FSIs (47,48) (Figure S1D,E).…”