title: Ventral tegmental area glutamate neurons co-release GABA and promote positive reinforcement.
abstract: In addition to dopamine neurons, the ventral tegmental area (VTA) contains GABA-, glutamate- and co-releasing neurons, and recent reports suggest a complex role for the glutamate neurons in behavioural reinforcement. We report that optogenetic stimulation of VTA glutamate neurons or terminals serves as a positive reinforcer on operant behavioural assays. Mice display marked preference for brief over sustained VTA glutamate neuron stimulation resulting in behavioural responses that are notably distinct from dopamine neuron stimulation and resistant to dopamine receptor antagonists. Whole-cell recordings reveal EPSCs following stimulation of VTA glutamate terminals in the nucleus accumbens or local VTA collaterals; but reveal both excitatory and monosynaptic inhibitory currents in the ventral pallidum and lateral habenula, though the net effects on postsynaptic firing in each region are consistent with the observed rewarding behavioural effects. These data indicate that VTA glutamate neurons co-release GABA in a projection-target-dependent manner and that their transient activation drives positive reinforcement.
authors.affiliation: Department of Neurosciences, University of California, San Diego, La Jolla, California 92093, USA.
authors.forename: Ji Hoon
authors.initials: JH
authors.lastname: Yoo
authors.affiliation: Department of Neurosciences, University of California, San Diego, La Jolla, California 92093, USA.
authors.forename: Vivien
authors.initials: V
authors.lastname: Zell
authors.affiliation: Biomedical Sciences Graduate Program, University of California, San Diego, La Jolla, California 92093, USA.
authors.forename: Navarre
authors.initials: N
authors.lastname: Gutierrez-Reed
authors.affiliation: Department of Neurosciences, University of California, San Diego, La Jolla, California 92093, USA.
authors.forename: Johnathan
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Neurosciences, University of California, San Diego, La Jolla, California 92093, USA.
authors.forename: Reed
authors.initials: R
authors.lastname: Ressler
authors.affiliation: Department of Neurosciences, University of California, San Diego, La Jolla, California 92093, USA.
authors.forename: Mohammad Ali
authors.initials: MA
authors.lastname: Shenasa
authors.affiliation: Department of Neurosciences, University of California, San Diego, La Jolla, California 92093, USA.
authors.forename: Alexander B
authors.initials: AB
authors.lastname: Johnson
authors.affiliation: Neuroscience Graduate Program, University of California, San Diego, La Jolla, California 92093, USA.
authors.forename: Kathryn H
authors.initials: KH
authors.lastname: Fife
authors.affiliation: Department of Neurosciences, University of California, San Diego, La Jolla, California 92093, USA.
authors.forename: Lauren
authors.initials: L
authors.lastname: Faget
authors.affiliation: Department of Neurosciences, University of California, San Diego, La Jolla, California 92093, USA.
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Hnasko
mesh_terms: D000818:Animals; D003216:Conditioning, Operant / Q000502:physiology*; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology*; D059330:GABAergic Neurons / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism*; D051379:Mice; D009474:Neurons / Q000378:metabolism*; D009714:Nucleus Accumbens / Q000166:cytology / Q000378:metabolism*; D062308:Optogenetics; D018408:Patch-Clamp Techniques; D012054:Reinforcement, Psychology; D017557:Ventral Tegmental Area / Q000166:cytology / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid