title: VTA glutamatergic inputs to nucleus accumbens drive aversion by acting on GABAergic interneurons.
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.
authors.affiliation: Neuronal Networks Section, Integrative Neuroscience Research Branch, US National Institute on Drug Abuse, Baltimore, Maryland, USA.
authors.forename: Jia
authors.initials: J
authors.lastname: Qi
authors.affiliation: Neuronal Networks Section, Integrative Neuroscience Research Branch, US National Institute on Drug Abuse, Baltimore, Maryland, USA.
authors.forename: Shiliang
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Neuronal Networks Section, Integrative Neuroscience Research Branch, US National Institute on Drug Abuse, Baltimore, Maryland, USA.
authors.forename: Hui-Ling
authors.initials: HL
authors.lastname: Wang
authors.affiliation: Neuronal Networks Section, Integrative Neuroscience Research Branch, US National Institute on Drug Abuse, Baltimore, Maryland, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Barker
authors.affiliation: Neuronal Networks Section, Integrative Neuroscience Research Branch, US National Institute on Drug Abuse, Baltimore, Maryland, USA.
authors.forename: Jorge
authors.initials: J
authors.lastname: Miranda-Barrientos
authors.affiliation: Neuronal Networks Section, Integrative Neuroscience Research Branch, US National Institute on Drug Abuse, Baltimore, Maryland, USA.
authors.forename: Marisela
authors.initials: M
authors.lastname: Morales
mesh_terms: D000818:Animals; D001362:Avoidance Learning / Q000502:physiology*; D018492:Dopamine Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D059290:Dopaminergic Neurons / Q000502:physiology; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D018756:GABA Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D059330:GABAergic Neurons / Q000502:physiology*; D018698:Glutamic Acid / Q000502:physiology*; D007395:Interneurons / Q000502:physiology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008845:Microinjections; D009433:Neural Inhibition / Q000502:physiology; D009434:Neural Pathways / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D017557:Ventral Tegmental Area / Q000502:physiology*
chemical_list: D018492:Dopamine Antagonists; D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D018698:Glutamic Acid