Neuronal phenotype defined by transcriptome-wide bursting kinetics in pyramidal and fast-spiking cells

ABSTRACT Single-cell sequencing revealed the transcriptional heterogeneity of neurons and introduced transcriptome-defined neuron types and subtypes. Temporal recordings of gene transcription showed that mRNA synthesis is arranged into transcriptional bursts which can be characterized by kinetic parameters. Here, we selected two distinct, functionally homogenous, and electrophysiologically well-defined neuronal cell types – the pyramidal cells and fast-spiking interneurons – for transcriptional burst analysis. Hierarchical clustering based on electrophysiological parameters recovered these cell types. In contrast, clustering based on transcripts failed to differentiate these neuronal phenotypes. We applied mathematical models to analyze burst kinetics of fast-spiking and pyramidal cells to explore the transcriptional underpinning of their distinct physiological functions. We found that inferred burst kinetic parameters are distinct measures of gene expression from average mRNA counts. Based on our results, we suggest that burst kinetics can be considered as a component of transcriptome-defined neuronal phenotype besides mRNA counts.