Mapping projections of molecularly defined dopamine neuron subtypes using intersectional genetic approaches

Jean Francois Poulin, Giuliana Caronia, Caitlyn Hofer, Qiaoling Cui, Brandon Helm, Charu Ramakrishnan, C. Savio Chan, Daniel A. Dombeck, Karl Deisseroth, Rajeshwar Awatramani*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

250 Scopus citations

Abstract

Midbrain dopamine (DA) neurons have diverse functions that can in part be explained by their heterogeneity. Although molecularly distinct subtypes of DA neurons have been identified by single-cell gene expression profiling, fundamental features such as their projection patterns have not been elucidated. Progress in this regard has been hindered by the lack of genetic tools for studying DA neuron subtypes. Here we develop intersectional genetic labeling strategies, based on combinatorial gene expression, to map the projections of molecularly defined DA neuron subtypes. We reveal distinct genetically defined dopaminergic pathways arising from the substantia nigra pars compacta and from the ventral tegmental area that innervate specific regions of the caudate putamen, nucleus accumbens and amygdala. Together, the genetic toolbox and DA neuron subtype projections presented here constitute a resource that will accelerate the investigation of this clinically significant neurotransmitter system.

Original languageEnglish (US)
Pages (from-to)1260-1271
Number of pages12
JournalNature neuroscience
Volume21
Issue number9
DOIs
StatePublished - Sep 1 2018

Funding

The authors wish to thank S. Ganguli, M. Jurado and I. Oksuz for technical assistance, S. Pieraut and A. Maximov for help with trimethropin injection protocol, and X. Zhuang (University of Chicago) and B. Lowell (Harvard) for sharing mouse strains. This work was supported by NIH grants R01NS06977 and R01NS047085 to C.S.C.; NIH grant R01MH110556-01A1 to D.A.D.; NIH grants R01MH110556-01A1, 1R21NS072703-01A1 and R01NS096240-01 and NARSAD and Paul Ruby Foundation grants to R.A.; and grants from MJFF and CIHR to J.-F.P.

ASJC Scopus subject areas

  • General Neuroscience

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