Abstract
GABAergic interneuron diversity is a key feature in the brain that helps to create different brain activity patterns and behavioral states. Cell type classification schemes—based on anatomical, physiological and molecular features—have provided us with a detailed understanding of the distinct types that constitute this diversity and their contribution to brain function. Over recent years, the utility of single-cell RNAseq has majorly complemented this existing framework, vastly expanding our knowledge base, particularly regarding molecular features. Single-cell gene-expression profiles of tens of thousands of GABAergic cells from many different types are now available. The analysis of these data has shed new lights onto previous classification principles and illuminates a path towards a deeper understanding of molecular hallmarks behind interneuron diversity. A large part of such molecular features is synapse-related. These include ion channels and receptors, as well as key synaptic organizers and trans-synaptic signaling molecules. Increasing evidence suggests that transcriptional and post-transcriptional modifications further diversify these molecules and generate cell type-specific features. Thus, unraveling the cell type-specific nature of gene-isoform expression will be a key in cell type classification. This review article discusses progress in the transcriptomic survey of interneurons and insights that have begun to manifest from isoform-level analyses.
Highlights
The activity of excitatory neurons is shaped by a highly diverse population of GABAergic interneurons (Klausberger and Somogyi, 2008; Rudy et al, 2011; Kepecs and Fishell, 2014)
Developmental origin has emerged as another distinctive feature for describing GABAergic cells (Pelkey et al, 2017; Wamsley and Fishell, 2017; Lim et al, 2018)
Deep Survey of GABAergic Interneurons unique features exist for every potential distinct cellular identity or if, continuous modes of variables are needed to cover the diversity of interneurons, is an ongoing matter of debate
Summary
The activity of excitatory neurons is shaped by a highly diverse population of GABAergic interneurons (Klausberger and Somogyi, 2008; Rudy et al, 2011; Kepecs and Fishell, 2014). Deep Survey of GABAergic Interneurons unique features exist for every potential distinct cellular identity or if, continuous modes of variables are needed to cover the diversity of interneurons, is an ongoing matter of debate. The immense power of transcriptomic surveys has been highlighted by their capacity to closely match previous cell type classifications, and in facilitating the discovery of potential new cell types These surveys disclose additional layers of complexity. There is a high level of granularity in identifying single cells, which makes their classification still challenging In addition to their ability to detect differential gene expression levels, transcriptomic surveys began to reveal insights into cell type-specific transcriptional and post-transcriptional modifications, such as differential promoter usage and alternative splicing. We will elaborate on the importance of introducing the analysis of gene-isoform expression levels in cell type taxonomies and how this could facilitate the classification of cell type identities
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