The biological basis and mechanistic framework of neuronal identity and diversity have been elusive. A communication-based approach to defining neuron types operationally by input/output relationships has been proposed (Lerner et al., 2016). Here, through single cell transcriptome analysis of phenotype-characterized GABAergic neurons, we have discovered that transcriptional architecture of input/output (I/O) synaptic communication may underlie neuronal identity. This overarching and mechanistic definition of neuronal identity integrates cell phenotypes along multiple axes and provides a foundation for understanding neuronal diversity and achieving biological (i.e. beyond operational) classification.
