Glutamatergic and dopaminergic neurons in the mouse ventral tegmental area. (9th January 2015)

• Record Type: Journal Article
• Authors: Yamaguchi, Tsuyoshi; Qi, Jia; Wang, Hui‐Ling; Zhang, Shiliang; Morales, Marisela
• Is Part Of: European journal of neuroscience. Volume 41:Number 6(2015:Mar.)
• Page Start: 760
• Page End: 772
• Publication Date: 2015-01-09
• Subjects: interpeduncular nucleus -- lateral habenula -- optogenetics reward -- ventral tegmental area -- VGluT2; Nervous system -- Periodicals; 612.8
• DOI: 10.1111/ejn.12818
• Languages: English
• ISSNs: 0953-816X

Abstract

Abstract: The ventral tegmental area (VTA) comprises dopamine (DA), γ‐aminobutyric acid (GABA) and glutamate (Glu) neurons. Some rat VTA Glu neurons, expressing vesicular glutamate transporter 2 (VGluT2), co‐express tyrosine hydroxylase (TH). While transgenic mice are now being used in attempts to determine the role of VGluT2/TH neurons in reward and neuronal signaling, such neurons have not been characterized in mouse tissue. By cellular detection of VGluT2 mRNA and TH immunoreactivity (TH‐IR), we determined the cellular expression of VGluT2 mRNA within VTA TH‐IR neurons in the mouse. We found that some mouse VGluT2 neurons coexpressed TH‐IR, but their frequency was lower than in the rat. To determine whether low expression of TH mRNA or TH‐IR accounts for this low frequency, we evaluated VTA cellular coexpression of TH transcripts and TH protein. Within the medial aspects of the VTA, some neurons expressed TH mRNA but lacked TH‐IR; among them a subset coexpressed VGluT2 mRNA. To determine if lack of VTA TH‐IR was due to TH trafficking, we tagged VTA TH neurons by Cre‐inducible expression of mCherry in TH::Cre mice. By dual immunofluorescence, we detected axons containing mCherry, but lacking TH‐IR, in the lateral habenula, indicating that low frequency of VGluT2 mRNA (+)/TH‐IR (+) neurons in the mouse is due to lack of synthesis of TH protein, rather than TH protein trafficking. In conclusion, VGluT2 neurons are present in the rat and mouse VTA, but they differ in the populations of VGluT2/TH and TH neurons. Under normal conditions, the translation of TH protein is suppressed in the mouse mesohabenular TH neurons. Abstract : Unlike the A10 area of the rat, the mouse A10 area contains a group of TH and VGluT2/TH neurons that do not seem to synthesize dopamine in the adult under normal conditions, as they lack detectable levels of TH protein. By double immunofluorescence, we found mesohabenular fibers expressing mCherry under the TH promoter contain high levels of mCherry signal, but lack detectable levels of TH protein, indicating that the lateral habenula is targeted by TH mRNA(+)/TH protein(−) neurons. In contrast, the A10 innervations to the nucleus accumbens containing mCherry also contained TH‐protein.