title: Dopaminergic terminals in the nucleus accumbens but not the dorsal striatum corelease glutamate.
abstract: Coincident signaling by dopamine and glutamate is thought to be crucial for a variety of motivated behaviors. Previous work has suggested that some midbrain dopamine neurons are themselves capable of glutamate corelease, but this phenomenon remains poorly understood. Here, we expressed the light-activated cation channel Channelrhodopsin-2 (ChR2) in genetically defined midbrain dopamine neurons to stimulate exocytosis specifically from dopaminergic terminals in both the nucleus accumbens (NAc) shell and dorsal striatum of brain slices from adult mice. Optical activation resulted in robust glutamate-mediated EPSCs in all medium spiny neurons examined in the NAc shell. In contrast, optically evoked glutamatergic currents were nearly undetectable in the dorsal striatum. Further, we used a conditional knock-out mouse lacking vesicular glutamate transporter 2 (VGLUT2) specifically in dopamine neurons to determine whether VGLUT2 is required for the exocytotic release of glutamate from dopamine neurons. Our data show that conditional knock-out completely abolished all optically evoked glutamate release. These results provide definitive physiological evidence for VGLUT2-mediated glutamate release by mature dopamine neurons projecting to the NAc shell, but not to the dorsal striatum. Thus, the unique ability of NAc-projecting dopamine neurons to synchronously activate both dopamine and glutamate receptors may have crucial implications for the ability to respond to motivationally significant stimuli.
authors.affiliation: Ernest Gallo Clinic and Research Center, University of California, San Francisco, Emeryville, California 94608, USA.
authors.forename: Garret D
authors.initials: GD
authors.lastname: Stuber
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Hnasko
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Britt
authors.forename: Robert H
authors.initials: RH
authors.lastname: Edwards
authors.forename: Antonello
authors.initials: A
authors.lastname: Bonci
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D001703:Biophysics; D000075402:Channelrhodopsins; D003342:Corpus Striatum / Q000166:cytology / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000494:pharmacology; D004558:Electric Stimulation / Q000379:methods; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000235:genetics; D005089:Exocytosis / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics; D018698:Glutamic Acid / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009714:Nucleus Accumbens / Q000166:cytology*; D018408:Patch-Clamp Techniques; D010775:Photic Stimulation / Q000379:methods; D017729:Presynaptic Terminals / Q000378:metabolism*; D011810:Quinoxalines / Q000494:pharmacology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D050599:Vesicular Glutamate Transport Protein 2 / Q000172:deficiency
chemical_list: D001552:Benzazepines; D000075402:Channelrhodopsins; D018492:Dopamine Antagonists; D018691:Excitatory Amino Acid Antagonists; D011810:Quinoxalines; C534628:SCH 23390; C493477:Slc17a6 protein, mouse; D050599:Vesicular Glutamate Transport Protein 2; D018698:Glutamic Acid; C056723:FG 9041; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine