title: Glutamate corelease promotes growth and survival of midbrain dopamine neurons.
abstract: Recent studies have proposed that glutamate corelease by mesostriatal dopamine (DA) neurons regulates behavioral activation by psychostimulants. How and when glutamate release by DA neurons might play this role remains unclear. Considering evidence for early expression of the type 2 vesicular glutamate transporter in mesencephalic DA neurons, we hypothesized that this cophenotype is particularly important during development. Using a conditional gene knock-out approach to selectively disrupt the Vglut2 gene in mouse DA neurons, we obtained in vitro and in vivo evidence for reduced growth and survival of mesencephalic DA neurons, associated with a decrease in the density of DA innervation in the nucleus accumbens, reduced activity-dependent DA release, and impaired motor behavior. These findings provide strong evidence for a functional role of the glutamatergic cophenotype in the development of mesencephalic DA neurons, opening new perspectives into the pathophysiology of neurodegenerative disorders involving the mesostriatal DA system.
authors.affiliation: Department of Pharmacology, and Groupe de Recherche sur le Système Nerveux Central, Faculty of Medicine, Université de Montréal, Montréal, Québec, Canada H3C 3J7.
authors.forename: Guillaume M
authors.initials: GM
authors.lastname: Fortin
authors.forename: Marie-Josée
authors.initials: MJ
authors.lastname: Bourque
authors.forename: Jose Alfredo
authors.initials: JA
authors.lastname: Mendez
authors.forename: Damiana
authors.initials: D
authors.lastname: Leo
authors.forename: Karin
authors.initials: K
authors.lastname: Nordenankar
authors.forename: Carolina
authors.initials: C
authors.lastname: Birgner
authors.forename: Emma
authors.initials: E
authors.lastname: Arvidsson
authors.forename: Vladimir V
authors.initials: VV
authors.lastname: Rymar
authors.forename: Noémie
authors.initials: N
authors.lastname: Bérubé-Carrière
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Claveau
authors.forename: Laurent
authors.initials: L
authors.lastname: Descarries
authors.forename: Abbas F
authors.initials: AF
authors.lastname: Sadikot
authors.forename: Åsa
authors.initials: Å
authors.lastname: Wallén-Mackenzie
authors.forename: Louis-Éric
authors.initials: LÉ
authors.lastname: Trudeau
mesh_terms: D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000378:metabolism*; D018698:Glutamic Acid / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008636:Mesencephalon / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects; D045442:Rotarod Performance Test; D050599:Vesicular Glutamate Transport Protein 2 / Q000235:genetics / Q000378:metabolism
chemical_list: D000697:Central Nervous System Stimulants; D050599:Vesicular Glutamate Transport Protein 2; D018698:Glutamic Acid; D000661:Amphetamine