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- Title
Glutamate Corelease Promotes Growth and Survival of Midbrain Dopamine Neurons.
- Authors
Fortin, Guillaume M.; Bourque, Marie-Josée; Mendez, Jose Alfredo; Leo, Damiana; Nordenankar, Karin; Birgner, Carolina; Arvidsson, Emma; Rymar, Vladimir V.; Bérubé-Carrière, Noémie; Claveau, Anne-Marie; Descarries, Laurent; Sadikot, Abbas F.; Wallén-Mackenzie, Âsa; Trudeau, Louis-Éric
- 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.
- Subjects
PHYSIOLOGICAL effects of glutamic acid; NEURON development; DOPAMINERGIC neurons; NUCLEUS accumbens; NEURAL physiology; LABORATORY mice
- Publication
Journal of Neuroscience, 2012, Vol 32, Issue 48, p17477
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.1939-12.2012