TY - JOUR
T1 - Defining midbrain dopaminergic neuron diversity by single-cell gene expression profiling
AU - Poulin, Jean Francois
AU - Zou, Jian
AU - Drouin-Ouellet, Janelle
AU - Kim, Kwang Youn A.
AU - Cicchetti, Francesca
AU - Awatramani, Rajeshwar B.
N1 - Funding Information:
The authors would like to thank Jennifer Darnell and Jason McKinney (Fluidigm) for technical assistance. The authors thank Dr. Richard J. Miller and Dr. D. James Surmeier for useful comments on the manuscript. This research was supported by R21 (1R21NS072703-01) and Northwestern Memorial Foundation (Paul Ruby Foundation for Parkinson’s Research) grants to R.B.A. This research was also supported by FRSQ, MJFF, and CIHR grants to J.-F.P.; a Paul Ruby Foundation grant to J.Z.; and a FRSQ grant to J.D.-O. K.-Y.A.K. would like to acknowledge NIH CTSA funding to Northwestern University Feinberg School of Medicine (UL1 TR000150 and UL1 RR025741). F.C. is a recipient of a National Research Career award from the Fonds de Recherche du Québec en Santé, providing salary support and funding.
Publisher Copyright:
© 2014 The Authors.
PY - 2014
Y1 - 2014
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84908436879&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84908436879&partnerID=8YFLogxK
U2 - 10.1016/j.celrep.2014.10.008
DO - 10.1016/j.celrep.2014.10.008
M3 - Article
C2 - 25437550
AN - SCOPUS:84908436879
SN - 2211-1247
VL - 9
SP - 930
EP - 943
JO - Cell Reports
JF - Cell Reports
IS - 3
ER -