Defining midbrain dopaminergic neuron diversity by single-cell gene expression profiling

Research output: Contribution to journalArticle

Abstract

Effective approaches to neuropsychiatric disorders require detailed understanding of the cellular composition and circuitry of the complex mammalian brain. Here, we present a paradigm for deconstructing the diversity of neurons defined by a specific neurotransmitter using a microfluidic dynamic array to simultaneously evaluate the expression of 96 genes in single neurons. With this approach, we successfully identified multiple molecularly distinct dopamine neuron subtypes and localized them in the adult mouse brain. To validate the anatomical and functional correlates of molecular diversity, we provide evidence that one Vip+ subtype, located in the periaqueductal region, has a discrete projection field within the extended amygdala. Another Aldh1a1+ subtype, located in the substantia nigra, is especially vulnerable in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of Parkinson's disease. Overall, this rapid, cost-effective approach enables the identification and classification of multiple dopamine neuron subtypes, with distinct molecular, anatomical, and functional properties.

Details

Authors
  • Jean-Francois Poulin
  • Jian Zou
  • Janelle Drouin-Ouellet
  • Kwang-Youn A Kim
  • Francesca Cicchetti
  • Rajeshwar B Awatramani
Organisations
External organisations
  • University of Cambridge
Research areas and keywords

Keywords

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine, Aging, Animals, Disease Models, Animal, Dopaminergic Neurons, Gene Expression Profiling, High-Throughput Screening Assays, Mesencephalon, Mice, Inbred C57BL, Parkinson Disease, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't
Original languageEnglish
Pages (from-to)930-43
Number of pages14
JournalCell Reports
Volume9
Issue number3
Publication statusPublished - 2014 Nov 6
Publication categoryResearch
Peer-reviewedYes