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Signal."],"published-print":{"date-parts":[[2026,8,18]]},"abstract":"<jats:p>Dopamine neurons in the ventral tegmental area (VTA) have roles in motivation, learning, and psychiatric disorders. We found that genetically defined VTA dopamine neuron subtypes had distinct electrophysiological properties, neuronal signaling dynamics in response to reward- and aversion-related stimuli, and roles in somatic optogenetically induced reward dependent on the neurotransmitters they released. Nonglutamate-dopamine neurons increased activity after reward-related stimuli and decreased activity after the omission of an expected reward (negative reward prediction error) and aversion-related stimuli. Glutamate-dopamine and glutamate-only (nonGABAergic and nondopaminergic) neurons were activated by both rewarding and aversive events, but only glutamate-dopamine neurons had sustained cue-induced reward signaling. Recordings of all dopamine neurons without considering glutamate cotransmission showed mixed population responses during prediction error and aversive stimuli that obscured the distinct signaling patterns of its constituent subpopulations. Although the examined cell types largely differ in mediolateral location, cell-type identity better accounted for functional differences than mediolateral location. Glutamate-dopamine neurons were more excitable than nonglutamate-dopamine neurons. Glutamate-dopamine and nonglutamate-dopamine axons had similar but not identical dopamine release dynamics in the nucleus accumbens. Only nonglutamate-dopamine neurons supported somatic optogenetically induced reward and reinforcement. In glutamate-dopamine neurons, the dopamine synthetic enzyme TH contributed to associative learning of aversive or less-beneficial outcomes, whereas the vesicular glutamate transporter VGLUT2 contributed to reward- and exploration-related vigor. Our results suggest that glutamate cotransmission is a distinguishing feature of VTA dopamine neuron signaling patterns and roles in natural reward- or aversion-motivated behavior.<\/jats:p>","DOI":"10.1126\/scisignal.aee2028","type":"journal-article","created":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T17:58:07Z","timestamp":1787075887000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Distinct properties of glutamate-dopamine, nonglutamate-dopamine, and glutamate-only ventral tegmental area neurons"],"prefix":"10.1126","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2258-1742","authenticated-orcid":true,"given":"Emily D.","family":"Pr\u00e9vost","sequence":"first","affiliation":[{"name":"Department of Psychology and Neuroscience, University of Colorado, 2860 Wilderness Pl, Boulder, CO 80301, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-4483-4241","authenticated-orcid":true,"given":"Lucy A.","family":"Ward","sequence":"additional","affiliation":[{"name":"Department of Psychology and Neuroscience, University of Colorado, 2860 Wilderness Pl, Boulder, CO 80301, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-0550-690X","authenticated-orcid":true,"given":"Daniel","family":"Alas","sequence":"additional","affiliation":[{"name":"Department of Psychology and Neuroscience, University of Colorado, 2860 Wilderness Pl, Boulder, CO 80301, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-8872-5626","authenticated-orcid":true,"given":"Giulia","family":"A. 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