title: Characterization of A11 neurons projecting to the spinal cord of mice.
abstract: The hypothalamic A11 region has been identified in several species including rats, mice, cats, monkeys, zebrafish, and humans as the primary source of descending dopamine (DA) to the spinal cord. It has been implicated in the control of pain, modulation of the spinal locomotor network, restless leg syndrome, and cataplexy, yet the A11 cell group remains an understudied dopaminergic (DAergic) nucleus within the brain. It is unclear whether A11 neurons in the mouse contain the full complement of enzymes consistent with traditional DA neuronal phenotypes. Given the abundance of mouse genetic models and tools available to interrogate specific neural circuits and behavior, it is critical first to fully understand the phenotype of A11 cells. We provide evidence that, in addition to tyrosine hydroxylase (TH) that synthesizes L-DOPA, neurons within the A11 region of the mouse contain aromatic L-amino acid decarboxylase (AADC), the enzyme that converts L-DOPA to dopamine. Furthermore, we show that the A11 neurons contain vesicular monoamine transporter 2 (VMAT2), which is necessary for packaging DA into vesicles. On the contrary, A11 neurons in the mouse lack the dopamine transporter (DAT). In conclusion, our data suggest that A11 neurons are DAergic. The lack of DAT, and therefore the lack of a DA reuptake mechanism, points to a longer time of action compared to typical DA neurons.
authors.affiliation: Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Koblinger
authors.affiliation: Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Tamás
authors.initials: T
authors.lastname: Füzesi
authors.affiliation: Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada; Department of Comparative Biology and Experimental Medicine, University of Calgary, Calgary, Canada.
authors.forename: Jillian
authors.initials: J
authors.lastname: Ejdrygiewicz
authors.affiliation: Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada; Department of Comparative Biology and Experimental Medicine, University of Calgary, Calgary, Canada.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Krajacic
authors.affiliation: Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada; Department of Physiology and Pharmacology, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Jaideep S
authors.initials: JS
authors.lastname: Bains
authors.affiliation: Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada; Department of Physiology and Pharmacology, University of Calgary, Calgary, Alberta, Canada; Department of Comparative Biology and Experimental Medicine, University of Calgary, Calgary, Canada.
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Whelan
mesh_terms: D000818:Animals; D001142:Aromatic-L-Amino-Acid Decarboxylases / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000378:metabolism*; D006801:Humans; D007031:Hypothalamus / Q000166:cytology* / Q000378:metabolism; D007980:Levodopa / Q000378:metabolism; D051379:Mice; D013116:Spinal Cord / Q000166:cytology / Q000503:physiopathology*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D050493:Vesicular Monoamine Transport Proteins / Q000378:metabolism
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; D050493:Vesicular Monoamine Transport Proteins; D007980:Levodopa; D014446:Tyrosine 3-Monooxygenase; D001142:Aromatic-L-Amino-Acid Decarboxylases; D004298:Dopamine