Heterogeneous composition of dopamine neurons of the rat A10 region: molecular evidence for diverse signaling properties

Brain Struct Funct. 2013 Sep;218(5):1159-76. doi: 10.1007/s00429-012-0452-z. Epub 2012 Aug 29.


The A10 region contains different neurons: dopamine (expressing tyrosine hydroxylase; TH), GABA, glutamate-only (expressing the vesicular glutamate transporter 2; VGluT2), and TH-VGluT2 (coexpressing TH and VGluT2). We used three methods to investigate proteins necessary for the synthesis (aromatic L-amino acid decarboxylase, AADC) or transport (vesicular monoamine transporter; VMAT2 or dopamine transporter; DAT) of dopamine within TH neurons in the A10 region. By in situ hybridization-immunohistochemistry, we found that all TH neurons in the A10 region had AADC, but not all had VMAT2, DAT or D2 receptors (D2R). To determine whether TH-VGluT2 neurons account for TH neurons lacking these dopamine markers, we implemented an anatomical "mirror technique", and found that not all TH-VGluT2 neurons lacked VMAT2, DAT or D2R. Next, by quantitative RT-PCR of individual micro-dissected TH neurons, we discovered two classes of TH-VGluT2 and three classes of TH-only neurons with different latero-medial distribution. Some of the TH-VGluT2 neurons had both VMAT2 and DAT (TH-VGluT2 Class 1); others lacked detectable levels of both transporters (TH-VGluT2 Class 2). Most of the TH-only neurons contained VMAT2 and DAT (TH-only Class 1), a few had DAT without detectable VMAT2 (TH-only Class 2), and others lacked detectable levels of both transporters (TH-only Class 3). We concluded that (a) the majority of TH neurons lacking DAT are TH-VGluT2 neurons, (b) very few TH-only neurons express DAT without VMAT2, and (c) TH-VGluT2 neurons lacking DAT also lack VMAT2. Thus, the A10 region contains dopamine neurons with differential compartmentalization and unique signaling properties.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Aromatic-L-Amino-Acid Decarboxylases / metabolism
  • Dopamine / biosynthesis
  • Dopamine / metabolism*
  • Dopamine Plasma Membrane Transport Proteins / metabolism
  • Dopaminergic Neurons / cytology
  • Dopaminergic Neurons / enzymology
  • Dopaminergic Neurons / physiology*
  • Immunohistochemistry
  • In Situ Hybridization
  • Laser Capture Microdissection
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Real-Time Polymerase Chain Reaction
  • Signal Transduction / physiology*
  • Tyrosine 3-Monooxygenase / metabolism*
  • Ventral Tegmental Area / cytology*
  • Vesicular Monoamine Transport Proteins / metabolism


  • Dopamine Plasma Membrane Transport Proteins
  • Vesicular Monoamine Transport Proteins
  • Tyrosine 3-Monooxygenase
  • Aromatic-L-Amino-Acid Decarboxylases
  • Dopamine