Cocaine exposure enhances the activity of ventral tegmental area dopamine neurons via calcium-impermeable NMDARs

Meaghan Creed, Jennifer Kaufling, Giulia R. Fois, Marion Jalabert, Tifei Yuan, Christian Lüscher, Francois Georges, Camilla Bellone

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Potentiation of excitatory inputs onto dopamine neurons of the ventral tegmental area (VTA) induced by cocaine exposure allows remodeling of the mesocorticolimbic circuitry, which ultimately drives drug-adaptive behavior. This potentiation is mediated by changes in NMDAR and AMPAR subunit composition. It remains unknown how this synaptic plasticity affects the activity of dopamine neurons. Here, using rodents, we demonstrate that a single cocaine injection increases the firing rate and bursting activity of VTA dopamine neurons, and that these increases persist for 7 d. This enhanced activity depends on the insertion of low-conductance, Ca2+-impermeable NMDARs that contain GluN3A. Since such receptors are not capable of activating small-conductance potassium channels, the intrinsic excitability of VTA dopamine neurons increases. Activation of group I mGluRs rescues synaptic plasticity and restores small-conductance calcium-dependent potassium channel function, normalizing the firing activity of dopamine neurons. Our study characterizes a mechanism linking drug-evoked synaptic plasticity to neural activity, revealing novel targets for therapeutic interventions.

Original languageEnglish
Pages (from-to)10759-10768
Number of pages10
JournalJournal of Neuroscience
Volume36
Issue number42
DOIs
StatePublished - Oct 19 2016
Externally publishedYes

Keywords

  • Dopamine
  • Firing rate
  • GluN3A
  • NMDA

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    Creed, M., Kaufling, J., Fois, G. R., Jalabert, M., Yuan, T., Lüscher, C., Georges, F., & Bellone, C. (2016). Cocaine exposure enhances the activity of ventral tegmental area dopamine neurons via calcium-impermeable NMDARs. Journal of Neuroscience, 36(42), 10759-10768. https://doi.org/10.1523/JNEUROSCI.1703-16.2016