Development, wiring and function of dopamine neuron subtypes

ABSTRACT The midbrain dopamine (mDA) system is composed of molecularly and functionally distinct neuron subtypes that mediate specific behaviours and are linked to various brain diseases.

Considerable progress has been made in identifying mDA neuron subtypes, and recent work has begun to unveil how these neuronal subtypes develop and organize into functional brain structures.

This progress is important for further understanding the disparate physiological functions of mDA neurons and their selective vulnerability in disease, and will ultimately accelerate

therapy development. This Review discusses recent advances in our understanding of molecularly defined mDA neuron subtypes and their circuits, ranging from early developmental events, such

as neuron migration and axon guidance, to their wiring and function, and future implications for therapeutic strategies. Access through your institution Buy or subscribe This is a preview of

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* Log in * Learn about institutional subscriptions * Read our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS HOW CHANGES IN DOPAMINE D2 RECEPTOR LEVELS ALTER STRIATAL

CIRCUIT FUNCTION AND MOTIVATION Article 12 August 2021 A SINGLE-CELL TRAJECTORY ATLAS OF STRIATAL DEVELOPMENT Article Open access 03 June 2023 UNIQUE FUNCTIONAL RESPONSES DIFFERENTIALLY MAP

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The authors thank P. Lingor for input on the manuscript. Work on the dopamine system in the laboratory of the authors is supported by Stichting Parkinson Fonds, the Dutch Research Council

(NWO; ALW-VICI 865.14.004) and the NWO Gravitation programme BRAINSCAPES: A Roadmap from Neurogenetics to Neurobiology (NWO: 024.004.012) to R.J.P. The authors apologize to all investigators

whose research could not be appropriately cited owing to space limitations. AUTHOR INFORMATION Author notes * These authors contributed equally: Oxana Garritsen, Eljo Y. van Battum, Laurens

M. Grossouw. AUTHORS AND AFFILIATIONS * Department of Translational Neuroscience, UMC Utrecht Brain Center, University Medical Center, Utrecht University, Utrecht, Netherlands Oxana

Garritsen, Eljo Y. van Battum, Laurens M. Grossouw & R. Jeroen Pasterkamp Authors * Oxana Garritsen View author publications You can also search for this author inPubMed Google Scholar *

Eljo Y. van Battum View author publications You can also search for this author inPubMed Google Scholar * Laurens M. Grossouw View author publications You can also search for this author

inPubMed Google Scholar * R. Jeroen Pasterkamp View author publications You can also search for this author inPubMed Google Scholar CONTRIBUTIONS All authors contributed to all aspects of

the article. CORRESPONDING AUTHOR Correspondence to R. Jeroen Pasterkamp. ETHICS DECLARATIONS COMPETING INTERESTS The authors declare no competing interests. PEER REVIEW PEER REVIEW

INFORMATION _Nature Reviews Neuroscience_ thanks S. Blaess, L. Zweifel and the other, anonymous, reviewer(s) for their contribution to the peer review of this work. ADDITIONAL INFORMATION

PUBLISHER’S NOTE Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. GLOSSARY *

1-Methyl-4-phenyl-1,2,3,5-tetrahydropyridine Neurotoxin that upon intracerebral injection causes rapid degeneration of the substantia nigra and parkinsonian symptoms, a method used for

modelling (late-stage) Parkinson disease in animal models. * 1-Methyl-4-phenylpyridinium A toxic metabolite of 1-methyl-4-phenyl-1,2,3,5-tetrahydropyridine. * [3H]Thymidine Radioactive

thymidine analogue that is taken up when DNA is synthesized, used as a marker for cell proliferation. * Assembloid A fused region-specific organoid used to model interactions between

different tissue types or organs. * Axon guidance Process during which extrinsic molecules instruct the orientation of axonal growth through attraction and/or repulsion of the axon tip. *

Embryonic stem cells (ES cells). Pluripotent stem cells derived from the inner cell mass of blastocyst-stage embryos. * Floorplate A ventral organizer region along the midline of the neural

tube that regulates neuronal differentiation and positioning. * Genetic fate mapping Genetic labelling of ancestor cells and their descendants to map the anatomical and cellular origin of

cells of interest. * Induced pluripotent stem cells (iPS cells). Pluripotent stem cells that are generated through the reprogramming of somatic cells by expression of a set of transcription

factors. * Intersectional genetics Selective targeting of cells by exploiting the combinatorial expression of two or more genes to express genetically encoded recombinases that results in

the activation of proteins to label or manipulate cells. * Laser capture microdissection Laser- and microscope-assisted cutting that enables precise dissection of microregions within the

tissue of interest. * Lineage tracing The identification of cellular progeny at subsequent developmental stages and processes by labelling an ancestor (progenitor) cell. * Major

histocompatibility complex Cell surface proteins that present self-antigens to prevent an autoimmune response. * Marginal zone Cell-sparse, outermost zone of the neural tube or brain

containing primarily axons and glial cells. * Neuroblast An undifferentiated precursor cell in the central nervous system that will eventually develop into a fully differentiated neural

cell. * Organoids Stem cell-derived and self-assembled 3D cultures that represent key features of the represented organ. * Radial glia-like cells Cells that are positive for radial glia

markers in single-cell RNA sequencing datasets. * Radial migration Migration of cells along radial glia fibres away from the ventricular zone. * Ribo-tagging Tagging of ribosomal subunits to

enable immunopurification and downstream processing of ribosomes and attached mRNAs. * Single-cell RNA sequencing (scRNA-seq). Dissociation and isolation of individual cells followed by

sequencing of the RNA transcriptome per cell. * Single-nucleus RNA sequencing (snRNA-seq). Dissociation and isolation of individual nuclei followed by sequencing of the RNA transcriptome per

nucleus. * Slide-seq Processing of tissue sections on an indexed slide to label RNA transcripts so as to preserve their spatial origin. * Spatial transcriptomics Methods to assign cell

types (based on mRNA readouts) to their anatomical location in tissue sections. * Tangential migration Migration of cells along the medial–lateral axis, parallel to the ventricular surface

and orthogonal to radial glia fibres. * Ventricular zone A transient layer of tissue lining the ventricles of the central nervous system that contains neural stem cells. RIGHTS AND

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ARTICLE CITE THIS ARTICLE Garritsen, O., van Battum, E.Y., Grossouw, L.M. _et al._ Development, wiring and function of dopamine neuron subtypes. _Nat Rev Neurosci_ 24, 134–152 (2023).

https://doi.org/10.1038/s41583-022-00669-3 Download citation * Accepted: 15 December 2022 * Published: 18 January 2023 * Issue Date: March 2023 * DOI:

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