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

Jia Qi, Shiliang Zhang, Hui Ling Wang, David Barker, Jorge Miranda-Barrientos, Marisela Morales

Research output: Contribution to journalArticle

53 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)725-733
Number of pages9
JournalNature Neuroscience
Volume19
Issue number5
DOIs
StatePublished - May 1 2016
Externally publishedYes

Fingerprint

Ventral Tegmental Area
Nucleus Accumbens
Interneurons
Parvalbumins
Synapses
Neurons
alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
GABA Receptors
Drive
Dopaminergic Neurons
Dopamine Receptors
Glutamate Receptors
Reward
Synaptic Transmission
gamma-Aminobutyric Acid

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Cite this

Qi, Jia ; Zhang, Shiliang ; Wang, Hui Ling ; Barker, David ; Miranda-Barrientos, Jorge ; Morales, Marisela. / VTA glutamatergic inputs to nucleus accumbens drive aversion by acting on GABAergic interneurons. In: Nature Neuroscience. 2016 ; Vol. 19, No. 5. pp. 725-733.
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VTA glutamatergic inputs to nucleus accumbens drive aversion by acting on GABAergic interneurons. / Qi, Jia; Zhang, Shiliang; Wang, Hui Ling; Barker, David; Miranda-Barrientos, Jorge; Morales, Marisela.

In: Nature Neuroscience, Vol. 19, No. 5, 01.05.2016, p. 725-733.

Research output: Contribution to journalArticle

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