Defining midbrain dopaminergic neuron diversity by single-cell gene expression profiling
(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.
(Less)
- author
- Poulin, Jean-Francois ; Zou, Jian ; Drouin-Ouellet, Janelle LU ; Kim, Kwang-Youn A ; Cicchetti, Francesca and Awatramani, Rajeshwar B
- organization
- publishing date
- 2014-11-06
- type
- Contribution to journal
- publication status
- 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
-
- pmid:25437550
- 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
- 2024-06-14 18:14:42
@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}},
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}},
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}},
doi = {{10.1016/j.celrep.2014.10.008}},
volume = {{9}},
year = {{2014}},
}