Classification of Midbrain Dopamine Neurons Using Single-Cell Gene Expression Profiling Approaches

• Published in: Trends in neurosciences (Regular ed.) Vol. 43; no. 3; pp. 155 - 169
• Main Authors: Poulin, Jean-Francois, Gaertner, Zachary, Moreno-Ramos, Oscar Andrés, Awatramani, Rajeshwar
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.03.2020
• Subjects: Brain; cell type; Dopamine; Dopaminergic Neurons; dopaminergic system; Gene Expression Profiling; intersectional; Mesencephalon; molecular diversity; neuroanatomy; single-cell RNA-seq; single-cell RNA-seq; intersectional; dopaminergic system; molecular diversity; neuroanatomy; cell type
• ISSN: 0166-2236; 1878-108X
• DOI: 10.1016/j.tins.2020.01.004

Dysfunctional dopamine (DA) signaling has been associated with a broad spectrum of neuropsychiatric disorders, prompting investigations into how midbrain DA neuron heterogeneity may underpin this variety of behavioral symptoms. Emerging literature indeed points to functional heterogeneity even within anatomically defined DA clusters. Recognizing the need for a systematic classification scheme, several groups have used single-cell profiling to catalog DA neurons based on their gene expression profiles. We aim here not only to synthesize points of congruence but also to highlight key differences between the molecular classification schemes derived from these studies. In doing so, we hope to provide a common framework that will facilitate investigations into the functions of DA neuron subtypes in the healthy and diseased brain. Emerging literature has identified molecularly distinct midbrain dopamine (DA) neuron subtypes but their number, location, and defining markers are currently debated.Based on available studies, we propose seven putative DA neuron subtypes and elaborate on their characteristic features.We provide a common framework for understanding DA neuron diversity, and this will hopefully facilitate the study of DA neurons in a subtype-specific manner.