Deep Survey of GABAergic Interneurons: Emerging Insights From Gene-Isoform Transcriptomics

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.