Defining Midbrain Dopaminergic Neuron Diversity by Single-Cell Gene Expression Profiling
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 arra...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2014-11-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124714008626 |
| _version_ | 1811278028598149120 |
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| author | Jean-Francois Poulin Jian Zou Janelle Drouin-Ouellet Kwang-Youn A. Kim Francesca Cicchetti Rajeshwar B. Awatramani |
| author_facet | Jean-Francois Poulin Jian Zou Janelle Drouin-Ouellet Kwang-Youn A. Kim Francesca Cicchetti Rajeshwar B. Awatramani |
| author_sort | Jean-Francois Poulin |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-13T00:28:28Z |
| format | Article |
| id | doaj.art-f824f2fe3f5149439ad504f62eb771f4 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-04-13T00:28:28Z |
| publishDate | 2014-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-f824f2fe3f5149439ad504f62eb771f42022-12-22T03:10:33ZengElsevierCell Reports2211-12472014-11-019393094310.1016/j.celrep.2014.10.008Defining Midbrain Dopaminergic Neuron Diversity by Single-Cell Gene Expression ProfilingJean-Francois Poulin0Jian Zou1Janelle Drouin-Ouellet2Kwang-Youn A. Kim3Francesca Cicchetti4Rajeshwar B. Awatramani5Department of Neurology and the Center for Genetic Medicine, Northwestern University, Chicago, IL 60611, USADepartment of Neurology and the Center for Genetic Medicine, Northwestern University, Chicago, IL 60611, USAJohn van Geest Centre for Brain Repair, University of Cambridge, Cambridge CB2 0PY, UKDepartment of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USACentre de Recherche du CHU de Québec, Axe Neurosciences and Université Laval, Québec, QC G1V 4G2, CanadaDepartment of Neurology and the Center for Genetic Medicine, Northwestern University, Chicago, IL 60611, USAEffective 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.http://www.sciencedirect.com/science/article/pii/S2211124714008626 |
| spellingShingle | Jean-Francois Poulin Jian Zou Janelle Drouin-Ouellet Kwang-Youn A. Kim Francesca Cicchetti Rajeshwar B. Awatramani Defining Midbrain Dopaminergic Neuron Diversity by Single-Cell Gene Expression Profiling Cell Reports |
| title | Defining Midbrain Dopaminergic Neuron Diversity by Single-Cell Gene Expression Profiling |
| title_full | Defining Midbrain Dopaminergic Neuron Diversity by Single-Cell Gene Expression Profiling |
| title_fullStr | Defining Midbrain Dopaminergic Neuron Diversity by Single-Cell Gene Expression Profiling |
| title_full_unstemmed | Defining Midbrain Dopaminergic Neuron Diversity by Single-Cell Gene Expression Profiling |
| title_short | Defining Midbrain Dopaminergic Neuron Diversity by Single-Cell Gene Expression Profiling |
| title_sort | defining midbrain dopaminergic neuron diversity by single cell gene expression profiling |
| url | http://www.sciencedirect.com/science/article/pii/S2211124714008626 |
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