VTA glutamatergic inputs to nucleus accumbens drive aversion by acting on GABAergic interneurons

Nat Neurosci. 2016 May;19(5):725-733. doi: 10.1038/nn.4281. Epub 2016 Mar 28.

Abstract

The ventral tegmental area (VTA) is best known for its dopamine neurons, some of which project to nucleus accumbens (nAcc). However, the VTA also has glutamatergic neurons that project to nAcc. The function of the mesoaccumbens glutamatergic pathway remains unknown. Here we report that nAcc photoactivation of mesoaccumbens glutamatergic fibers promotes aversion. Although we found that these mesoaccumbens glutamatergic fibers lack GABA, the aversion evoked by their photoactivation depended on glutamate- and GABA-receptor signaling, and not on dopamine-receptor signaling. We found that mesoaccumbens glutamatergic fibers established multiple asymmetric synapses on single parvalbumin GABAergic interneurons and that nAcc photoactivation of these fibers drove AMPA-mediated cellular firing of parvalbumin GABAergic interneurons. These parvalbumin GABAergic interneurons in turn inhibited nAcc medium spiny output neurons, thereby controlling inhibitory neurotransmission in nAcc. To our knowledge, the mesoaccumbens glutamatergic pathway is the first glutamatergic input to nAcc shown to mediate aversion instead of reward, and the first pathway shown to establish excitatory synapses on nAcc parvalbumin GABAergic interneurons.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Avoidance Learning / physiology*
  • Dopamine Antagonists / administration & dosage
  • Dopamine Antagonists / pharmacology
  • Dopaminergic Neurons / physiology
  • Excitatory Amino Acid Antagonists / administration & dosage
  • Excitatory Amino Acid Antagonists / pharmacology
  • GABA Antagonists / administration & dosage
  • GABA Antagonists / pharmacology
  • GABAergic Neurons / physiology*
  • Glutamic Acid / physiology*
  • Interneurons / physiology*
  • Male
  • Mice
  • Mice, Transgenic
  • Microinjections
  • Neural Inhibition / physiology
  • Neural Pathways / physiology
  • Neurons / physiology*
  • Nucleus Accumbens / drug effects
  • Nucleus Accumbens / physiology*
  • Nucleus Accumbens / ultrastructure
  • Ventral Tegmental Area / physiology*

Substances

  • Dopamine Antagonists
  • Excitatory Amino Acid Antagonists
  • GABA Antagonists
  • Glutamic Acid