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

Poulin, Jean-Francois; Zou, Jian; Drouin-Ouellet, Janelle LU ; Kim, Kwang-Youn A; Cicchetti, Francesca and Awatramani, Rajeshwar B (2014) In Cell Reports 9(3). p.43-930
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.... (More)

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.

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published
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
in
Cell Reports
volume
9
issue
3
pages
14 pages
publisher
Cell Press
external identifiers
  • scopus:84908436879
ISSN
2211-1247
DOI
10.1016/j.celrep.2014.10.008
language
English
LU publication?
no
id
d437967b-824f-4656-a181-124fb772effe
date added to LUP
2016-11-22 09:01:52
date last changed
2017-11-19 04:35:02
@article{d437967b-824f-4656-a181-124fb772effe,
  abstract     = {<p>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.</p>},
  author       = {Poulin, Jean-Francois and Zou, Jian and Drouin-Ouellet, Janelle and Kim, Kwang-Youn A and Cicchetti, Francesca and Awatramani, Rajeshwar B},
  issn         = {2211-1247},
  keyword      = {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},
  language     = {eng},
  month        = {11},
  number       = {3},
  pages        = {43--930},
  publisher    = {Cell Press},
  series       = {Cell Reports},
  title        = {Defining midbrain dopaminergic neuron diversity by single-cell gene expression profiling},
  url          = {http://dx.doi.org/10.1016/j.celrep.2014.10.008},
  volume       = {9},
  year         = {2014},
}