Transcriptional Architecture of Synaptic Communication Delineates Cortical GABAergic Neuron Identity

Abstract

Understanding the organizational logic of neural circuits requires deciphering the biological basis of neuron type diversity and identity, but there is no consensus on defining a neuron type. We analyzed single cell transcriptomes of anatomically and physiologically characterized cortical ground truth populations and conducted a computational genomic screen for transcription profiles that distinguish them. We discovered that cardinal GABAergic neuron types are delineated by a transcriptional architecture that encodes their synaptic communication patterns. This architecture comprises 6 categories of ~40 gene families including cell adhesion molecules, transmitter-modulator receptors, ion channels, signaling proteins, neuropeptides and vesicular release components, and transcription factors. Combinatorial expression of select members across families shapes a multi-layered molecular scaffold along cell membrane that may customize synaptic connectivity patterns and input-output signaling properties. This molecular genetic framework of neuronal identity integrates cell phenotypes along multiple axes and provides a foundation for discovering and classifying neuron types.