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

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 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.

journal_name

Cell Rep

journal_title

Cell reports

authors

Poulin JF,Zou J,Drouin-Ouellet J,Kim KY,Cicchetti F,Awatramani RB

doi

10.1016/j.celrep.2014.10.008

subject

Has Abstract

pub_date

2014-11-06 00:00:00

pages

930-43

issue

3

issn

2211-1247

pii

S2211-1247(14)00862-6

journal_volume

9

pub_type

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