Glutamate corelease promotes growth and survival of midbrain dopamine neurons

J Neurosci. 2012 Nov 28;32(48):17477-91. doi: 10.1523/JNEUROSCI.1939-12.2012.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amphetamine / pharmacology
  • Animals
  • Cell Survival / drug effects
  • Cell Survival / physiology*
  • Cells, Cultured
  • Central Nervous System Stimulants / pharmacology
  • Dopaminergic Neurons / drug effects
  • Dopaminergic Neurons / metabolism*
  • Glutamic Acid / genetics
  • Glutamic Acid / metabolism*
  • Male
  • Mesencephalon / drug effects
  • Mesencephalon / metabolism*
  • Mice
  • Mice, Knockout
  • Motor Activity / drug effects
  • Rotarod Performance Test
  • Vesicular Glutamate Transport Protein 2 / genetics
  • Vesicular Glutamate Transport Protein 2 / metabolism


  • Central Nervous System Stimulants
  • Vesicular Glutamate Transport Protein 2
  • Glutamic Acid
  • Amphetamine