Transcriptional Architecture of Synaptic Communication Delineates GABAergic Neuron Identity

Cell. 2017 Oct 19;171(3):522-539.e20. doi: 10.1016/j.cell.2017.08.032. Epub 2017 Sep 21.


Understanding the organizational logic of neural circuits requires deciphering the biological basis of neuronal diversity and identity, but there is no consensus on how neuron types should be defined. We analyzed single-cell transcriptomes of a set of anatomically and physiologically characterized cortical GABAergic neurons and conducted a computational genomic screen for transcriptional profiles that distinguish them from one another. 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 the 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.

Keywords: GABAergic interneurons; MetaNeighbor; cell type; co-expression; gene family; network analysis; neuronal identity; single-cell transcriptomes; synaptic communication; transcriptional architecture.

MeSH terms

  • Animals
  • Cell Adhesion Molecules, Neuronal / metabolism
  • Extracellular Matrix / metabolism
  • GABAergic Neurons / cytology*
  • GABAergic Neurons / metabolism
  • Gene Expression Profiling*
  • Mice
  • Receptors, GABA / metabolism
  • Receptors, Ionotropic Glutamate / metabolism
  • Signal Transduction
  • Single-Cell Analysis*
  • Synapses
  • Transcription, Genetic
  • Zinc / metabolism
  • gamma-Aminobutyric Acid / metabolism


  • Cell Adhesion Molecules, Neuronal
  • Receptors, GABA
  • Receptors, Ionotropic Glutamate
  • gamma-Aminobutyric Acid
  • Zinc