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

2016; Nature Portfolio; Volume: 19; Issue: 5 Linguagem: Inglês

10.1038/nn.4281

1546-1726

Jia Qi, Shiliang Zhang, Huiling Wang, David J. Barker, Jorge Miranda‐Barrientos, Marisela Morales,

Neurotransmitter Receptor Influence on Behavior

The authors show that glutamatergic neurons, which are intermixed with dopaminergic neurons in the ventral tegmental area, establish multiple excitatory synapses on parvalbumin GABAergic interneurons in the nucleus accumbens. Activation of this glutamatergic mesoaccumbens pathway induces the release of GABA onto medium spiny neurons and drives aversion. 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.