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Vesicular glutamate transport promotes dopamine storage and glutamate corelease in vivo.

Neuron | Mar 11, 2010

Dopamine neurons in the ventral tegmental area (VTA) play an important role in the motivational systems underlying drug addiction, and recent work has suggested that they also release the excitatory neurotransmitter glutamate. To assess a physiological role for glutamate corelease, we disrupted the expression of vesicular glutamate transporter 2 selectively in dopamine neurons. The conditional knockout abolishes glutamate release from midbrain dopamine neurons in culture and severely reduces their excitatory synaptic output in mesoaccumbens slices. Baseline motor behavior is not affected, but stimulation of locomotor activity by cocaine is impaired, apparently through a selective reduction of dopamine stores in the projection of VTA neurons to ventral striatum. Glutamate co-entry promotes monoamine storage by increasing the pH gradient that drives vesicular monoamine transport. Remarkably, low concentrations of glutamate acidify synaptic vesicles more slowly but to a greater extent than equimolar Cl(-), indicating a distinct, presynaptic mechanism to regulate quantal size.

Pubmed ID: 20223200 RIS Download

Mesh terms: Adenosine Triphosphate | Analysis of Variance | Animals | Animals, Newborn | Catecholamines | Cell Line, Transformed | Chlorides | Choline | Cocaine | Corpus Striatum | Dopamine | Dopamine Uptake Inhibitors | Glutamic Acid | Green Fluorescent Proteins | Humans | Hydrogen-Ion Concentration | In Vitro Techniques | Luminescent Proteins | Membrane Potentials | Mice | Mice, Transgenic | Motor Activity | Neurons | Presynaptic Terminals | Rats | Serotonin | Synaptic Vesicles | Transfection | Tyrosine 3-Monooxygenase | Vesicular Glutamate Transport Protein 2

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Associated grants

  • Agency: NIDA NIH HHS, Id: P01 DA010154
  • Agency: NIDA NIH HHS, Id: P01 DA010154-14
  • Agency: NIDA NIH HHS, Id: P01 DA010154-140009
  • Agency: NIDA NIH HHS, Id: K01 DA026504
  • Agency: NIDA NIH HHS, Id: P01 DA010154-140002
  • Agency: Howard Hughes Medical Institute, Id: R01 MH050712-17
  • Agency: NIMH NIH HHS, Id: K01 DA026504-01A1
  • Agency: NIDA NIH HHS, Id: R01 DA017978
  • Agency: NIDA NIH HHS, Id: R01 MH050712
  • Agency: NIMH NIH HHS, Id: K02 DA000356
  • Agency: NIDA NIH HHS, Id:

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