Defining midbrain dopaminergic neuron diversity by single-cell gene profiling
Identifieur interne : 000B04 ( Main/Exploration ); précédent : 000B03; suivant : 000B05Defining midbrain dopaminergic neuron diversity by single-cell gene profiling
Auteurs : Jean-Francois Poulin ; Jian Zou ; Janelle Drouin-Ouellet [Royaume-Uni] ; Kwang-Youn A. Kim ; Francesca Cicchetti ; Rajeshwar B. AwatramaniSource :
- Cell reports [ 2211-1247 ] ; 2014.
English descriptors
- KwdEn :
- 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine, Aging (metabolism), Animals, Disease Models, Animal, Dopaminergic Neurons (classification), Dopaminergic Neurons (cytology), Dopaminergic Neurons (metabolism), Gene Expression Profiling, High-Throughput Screening Assays, Mesencephalon (cytology), Mice, Inbred C57BL, Parkinson Disease (pathology).
- MESH :
- chemical : 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine.
- classification : Dopaminergic Neurons.
- cytology : Dopaminergic Neurons, Mesencephalon.
- metabolism : Aging, Dopaminergic Neurons.
- pathology : Parkinson Disease.
- Animals, Disease Models, Animal, Gene Expression Profiling, High-Throughput Screening Assays, Mice, Inbred C57BL.
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 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.
Url:
DOI: 10.1016/j.celrep.2014.10.008
PubMed: 25437550
PubMed Central: 4251558
Affiliations:
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Le document en format XML
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<front><div type="abstract" xml:lang="en"><p id="P1">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 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>
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