It has been suggested that TH-VGluT2 neurons corelease dopamine and glutamate, however, it is unclear whether these neurons have proteins necessary for the synthesis (aromatic L-amino acid decarboxylase, AADC) or transport (vesicular monoamine transporter, VMAT2 or dopamine transporter, DAT) of dopamine. 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 2 classes of TH-VGluT2 and 3 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) and others lacked 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 VMAT2 (TH-only Class 2), and others lacked both VMAT2 and DAT (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 we provide evidence that the A10 region contains dopamine neurons with differential compartmentalization and unique signaling properties.

Project Start
Project End
Budget Start
Budget End
Support Year
7
Fiscal Year
2013
Total Cost
$1,146,296
Indirect Cost
Name
National Institute on Drug Abuse
Department
Type
DUNS #
City
State
Country
Zip Code
Qi, Jia; Zhang, Shiliang; Wang, Hui-Ling et al. (2016) VTA glutamatergic inputs to nucleus accumbens drive aversion by acting on GABAergic interneurons. Nat Neurosci 19:725-33
Barker, David J; Root, David H; Zhang, Shiliang et al. (2016) Multiplexed neurochemical signaling by neurons of the ventral tegmental area. J Chem Neuroanat 73:33-42
Root, David H; Hoffman, Alexander F; Good, Cameron H et al. (2015) Norepinephrine activates dopamine D4 receptors in the rat lateral habenula. J Neurosci 35:3460-9
Yamaguchi, Tsuyoshi; Qi, Jia; Wang, Hui-Ling et al. (2015) Glutamatergic and dopaminergic neurons in the mouse ventral tegmental area. Eur J Neurosci 41:760-72
Zhang, Shiliang; Qi, Jia; Li, Xueping et al. (2015) Dopaminergic and glutamatergic microdomains in a subset of rodent mesoaccumbens axons. Nat Neurosci 18:386-92
Mejias-Aponte, Carlos A; Ye, Changquan; Bonci, Antonello et al. (2015) A subpopulation of neurochemically-identified ventral tegmental area dopamine neurons is excited by intravenous cocaine. J Neurosci 35:1965-78
Volkow, Nora D; Morales, Marisela (2015) The Brain on Drugs: From Reward to Addiction. Cell 162:712-25
Trudeau, Louis-Eric; Hnasko, Thomas S; Wallén-Mackenzie, Asa et al. (2014) The multilingual nature of dopamine neurons. Prog Brain Res 211:141-64
Nordenankar, Karin; Smith-Anttila, Casey J A; Schweizer, Nadine et al. (2014) Increased hippocampal excitability and impaired spatial memory function in mice lacking VGLUT2 selectively in neurons defined by tyrosine hydroxylase promoter activity. Brain Struct Funct :
Morales, M; Root, D H (2014) Glutamate neurons within the midbrain dopamine regions. Neuroscience 282:60-8

Showing the most recent 10 out of 16 publications