Transcriptional Architecture of Synaptic Communication Delineates GABAergic Neuron Identity

Anirban Paul, Megan Crow, Ricardo Raudales, Miao He, Jesse Gillis, Z. Josh Huang

Research output: Contribution to journalArticle

96 Scopus citations

Abstract

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. GABAergic neuron types are distinguished by a transcriptional architecture that encodes their synaptic communication patterns.

Original languageEnglish (US)
Pages (from-to)522-539.e20
JournalCell
Volume171
Issue number3
DOIs
StatePublished - Oct 19 2017

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

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