title: Glutamate neurons are intermixed with midbrain dopamine neurons in nonhuman primates and humans.
abstract: The rodent ventral tegmental area (VTA) and substantia nigra pars compacta (SNC) contain dopamine neurons intermixed with glutamate neurons (expressing vesicular glutamate transporter 2; VGluT2), which play roles in reward and aversion. However, identifying the neuronal compositions of the VTA and SNC in higher mammals has remained challenging. Here, we revealed VGluT2 neurons within the VTA and SNC of nonhuman primates and humans by simultaneous detection of VGluT2 mRNA and tyrosine hydroxylase (TH; for identification of dopamine neurons). We found that several VTA subdivisions share similar cellular compositions in nonhuman primates and humans; their rostral linear nuclei have a high prevalence of VGluT2 neurons lacking TH; their paranigral and parabrachial pigmented nuclei have mostly TH neurons, and their parabrachial pigmented nuclei have dual VGluT2-TH neurons. Within nonhuman primates and humans SNC, the vast majority of neurons are TH neurons but VGluT2 neurons were detected in the pars lateralis subdivision. The demonstration that midbrain dopamine neurons are intermixed with glutamate or glutamate-dopamine neurons from rodents to humans offers new opportunities for translational studies towards analyzing the roles that each of these neurons play in human behavior and in midbrain-associated illnesses such as addiction, depression, schizophrenia, and Parkinson's disease.
authors.affiliation: Neuronal Networks Section, Integrative Neuroscience Research Branch, National Institute on Drug Abuse, 251 Bayview Blvd Suite 200, Baltimore, MD 21224, USA.
authors.forename: David H
authors.initials: DH
authors.lastname: Root
authors.affiliation: Neuronal Networks Section, Integrative Neuroscience Research Branch, National Institute on Drug Abuse, 251 Bayview Blvd Suite 200, Baltimore, MD 21224, USA.
authors.forename: Hui-Ling
authors.initials: HL
authors.lastname: Wang
authors.affiliation: Neuronal Networks Section, Integrative Neuroscience Research Branch, National Institute on Drug Abuse, 251 Bayview Blvd Suite 200, Baltimore, MD 21224, USA.
authors.forename: Bing
authors.initials: B
authors.lastname: Liu
authors.affiliation: Neuronal Networks Section, Integrative Neuroscience Research Branch, National Institute on Drug Abuse, 251 Bayview Blvd Suite 200, Baltimore, MD 21224, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Barker
authors.affiliation: Department of Psychology, Szent Borbála Hospital, H-2800, Tatabánya, Hungary.
authors.forename: László
authors.initials: L
authors.lastname: Mód
authors.affiliation: Laboratory of Cerebral Cortex Research, Institute of Experimental Medicine of the Hungarian Academy of Sciences, H-1083, Budapest, Hungary.
authors.forename: Péter
authors.initials: P
authors.lastname: Szocsics
authors.affiliation: Cerebral Microcirculation Section, Laboratory of Functional and Molecular Imaging, National Institute of Neurological Disorders and Stroke, 49 Convent Drive Bldg 49 Room 3A72, Bethesda, MD 20892-4478, USA.
authors.forename: Afonso C
authors.initials: AC
authors.lastname: Silva
authors.affiliation: Laboratory of Cerebral Cortex Research, Institute of Experimental Medicine of the Hungarian Academy of Sciences, H-1083, Budapest, Hungary.
authors.forename: Zsófia
authors.initials: Z
authors.lastname: Maglóczky
authors.affiliation: Neuronal Networks Section, Integrative Neuroscience Research Branch, National Institute on Drug Abuse, 251 Bayview Blvd Suite 200, Baltimore, MD 21224, USA.
authors.forename: Marisela
authors.initials: M
authors.lastname: Morales
mesh_terms: D000818:Animals; D002144:Callithrix; D004298:Dopamine / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D008297:Male; D008636:Mesencephalon / Q000166:cytology* / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D065842:Pars Compacta / Q000166:cytology / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics / Q000378:metabolism; D017557:Ventral Tegmental Area / Q000166:cytology / Q000378:metabolism; D050599:Vesicular Glutamate Transport Protein 2 / Q000235:genetics / Q000378:metabolism
chemical_list: D050599:Vesicular Glutamate Transport Protein 2; D018698:Glutamic Acid; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine