title: Midbrain Gene Screening Identifies a New Mesoaccumbal Glutamatergic Pathway and a Marker for Dopamine Cells Neuroprotected in Parkinson's Disease.
abstract: The ventral tegmental area (VTA) and substantia nigra pars compacta (SNc) of the midbrain are associated with Parkinson's disease (PD), schizophrenia, mood disorders and addiction. Based on the recently unraveled heterogeneity within the VTA and SNc, where glutamate, GABA and co-releasing neurons have been found to co-exist with the classical dopamine neurons, there is a compelling need for identification of gene expression patterns that represent this heterogeneity and that are of value for development of human therapies. Here, several unique gene expression patterns were identified in the mouse midbrain of which NeuroD6 and Grp were expressed within different dopaminergic subpopulations of the VTA, and TrpV1 within a small heterogeneous population. Optogenetics-coupled in vivo amperometry revealed a previously unknown glutamatergic mesoaccumbal pathway characterized by TrpV1-Cre-expression. Human GRP was strongly detected in non-melanized dopaminergic neurons within the SNc of both control and PD brains, suggesting GRP as a marker for neuroprotected neurons in PD. This study thus unravels markers for distinct subpopulations of neurons within the mouse and human midbrain, defines unique anatomical subregions within the VTA and exposes an entirely new glutamatergic pathway. Finally, both TRPV1 and GRP are implied in midbrain physiology of importance to neurological and neuropsychiatric disorders.
authors.affiliation: Department of Organismal Biology/Comparative Physiology, Uppsala University, S-752 36 Uppsala, Sweden.|Department of Neuroscience, Uppsala University, S-751 24 Uppsala, Sweden.
authors.forename: Thomas
authors.initials: T
authors.lastname: Viereckel
authors.affiliation: Oramacell, 75006 Paris, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Dumas
authors.affiliation: Department of Organismal Biology/Comparative Physiology, Uppsala University, S-752 36 Uppsala, Sweden.|Department of Anatomy and Neuroscience, University of Melbourne, Victoria 3010, Australia.
authors.forename: Casey J A
authors.initials: CJ
authors.lastname: Smith-Anttila
authors.affiliation: Department of Organismal Biology/Comparative Physiology, Uppsala University, S-752 36 Uppsala, Sweden.
authors.forename: Bianca
authors.initials: B
authors.lastname: Vlcek
authors.affiliation: Department of Organismal Biology/Comparative Physiology, Uppsala University, S-752 36 Uppsala, Sweden.
authors.forename: Zisis
authors.initials: Z
authors.lastname: Bimpisidis
authors.affiliation: Department of Neuroscience, Uppsala University, S-751 24 Uppsala, Sweden.
authors.forename: Malin C
authors.initials: MC
authors.lastname: Lagerström
authors.affiliation: Department of Organismal Biology/Comparative Physiology, Uppsala University, S-752 36 Uppsala, Sweden.
authors.forename: Åsa
authors.initials: Å
authors.lastname: Konradsson-Geuken
authors.affiliation: Department of Organismal Biology/Comparative Physiology, Uppsala University, S-752 36 Uppsala, Sweden.
authors.forename: Åsa
authors.initials: Å
authors.lastname: Wallén-Mackenzie
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D059290:Dopaminergic Neurons / Q000378:metabolism* / Q000473:pathology; D059330:GABAergic Neurons / Q000378:metabolism / Q000473:pathology; D019886:Gastrin-Releasing Peptide / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D062308:Optogenetics; D010300:Parkinson Disease / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D065842:Pars Compacta / Q000378:metabolism* / Q000473:pathology; D009435:Synaptic Transmission; D050916:TRPV Cation Channels / Q000235:genetics* / Q000378:metabolism; D017557:Ventral Tegmental Area / Q000378:metabolism* / Q000473:pathology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D004298:Dopamine; D019886:Gastrin-Releasing Peptide; D018698:Glutamic Acid; D009419:Nerve Tissue Proteins; D050916:TRPV Cation Channels; D005680:gamma-Aminobutyric Acid; C110701:Neurod6 protein, mouse; C494482:TRPV1 protein, human