title: Ultrastructural characterization of the mesostriatal dopamine innervation in mice, including two mouse lines of conditional VGLUT2 knockout in dopamine neurons.
abstract: Despite the increasing use of genetically modified mice to investigate the dopamine (DA) system, little is known about the ultrastructural features of the striatal DA innervation in the mouse. This issue is particularly relevant in view of recent evidence for expression of the vesicular glutamate transporter 2 (VGLUT2) by a subset of mesencephalic DA neurons in mouse as well as rat. We used immuno-electron microscopy to characterize tyrosine hydroxylase (TH)-labeled terminals in the core and shell of nucleus accumbens and the neostriatum of two mouse lines in which the Vglut2 gene was selectively disrupted in DA neurons (cKO), their control littermates, and C57BL/6/J wild-type mice, aged P15 or adult. The three regions were also examined in cKO mice and their controls of both ages after dual TH-VGLUT2 immunolabeling. Irrespective of the region, age and genotype, the TH-immunoreactive varicosities appeared similar in size, vesicular content, percentage with mitochondria, and exceedingly low frequency of synaptic membrane specialization. No dually labeled axon terminals were found at either age in control or in cKO mice. Unless TH and VGLUT2 are segregated in different axon terminals of the same neurons, these results favor the view that the glutamatergic cophenotype of mesencephalic DA neurons is more important during the early development of these neurons than for the establishment of their scarce synaptic connectivity. They also suggest that, in mouse even more than rat, the mesostriatal DA system operates mainly through non-targeted release of DA, diffuse transmission and the maintenance of an ambient DA level.
authors.affiliation: Department of Pathology and Cell Biology, Faculty of Medicine, C.P. 6128, Succursale Centre-Ville, Université de Montréal, Montréal, QC H3C 3J7, Canada.
authors.forename: Noémie
authors.initials: N
authors.lastname: Bérubé-Carrière
authors.forename: Ginette
authors.initials: G
authors.lastname: Guay
authors.forename: Guillaume M
authors.initials: GM
authors.lastname: Fortin
authors.forename: Klas
authors.initials: K
authors.lastname: Kullander
authors.forename: Lars
authors.initials: L
authors.lastname: Olson
authors.forename: Åsa
authors.initials: Å
authors.lastname: Wallén-Mackenzie
authors.forename: Louis-Eric
authors.initials: LE
authors.lastname: Trudeau
authors.forename: Laurent
authors.initials: L
authors.lastname: Descarries
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D003342:Corpus Striatum / Q000166:cytology* / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins / Q000172:deficiency*; D059290:Dopaminergic Neurons / Q000378:metabolism* / Q000648:ultrastructure*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016253:Microscopy, Immunoelectron; D009714:Nucleus Accumbens / Q000166:cytology* / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism / Q000648:ultrastructure; D050599:Vesicular Glutamate Transport Protein 2 / Q000172:deficiency*
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; C493477:Slc17a6 protein, mouse; D050599:Vesicular Glutamate Transport Protein 2; D014446:Tyrosine 3-Monooxygenase