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

Nat Neurosci. 2018 Sep;21(9):1260-1271. doi: 10.1038/s41593-018-0203-4. Epub 2018 Aug 13.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain Mapping / methods*
  • Caudate Nucleus / cytology
  • Caudate Nucleus / physiology
  • Cell Line
  • Dopaminergic Neurons / physiology*
  • Gene Expression Profiling
  • Mice
  • Mice, Inbred C57BL
  • Neural Pathways / anatomy & histology
  • Neural Pathways / physiology*
  • Nucleus Accumbens / cytology
  • Nucleus Accumbens / physiology
  • Olfactory Bulb / cytology
  • Olfactory Bulb / physiology
  • Substantia Nigra / cytology
  • Substantia Nigra / physiology