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    Midbrain Gene Screening Identifies a New Mesoaccumbal Glutamatergic Pathway and a Marker for Dopamine Cells Neuroprotected in Parkinson's Disease.

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    Author
    Viereckel, T; Dumas, S; Smith-Anttila, CJA; Vlcek, B; Bimpisidis, Z; Lagerström, MC; Konradsson-Geuken, Å; Wallén-Mackenzie, Å
    Date
    2016-10-20
    Source Title
    Scientific Reports
    Publisher
    Springer Science and Business Media LLC
    University of Melbourne Author/s
    SMITH-ANTTILA, CASEY
    Affiliation
    Anatomy and Neuroscience
    Metadata
    Show full item record
    Document Type
    Journal Article
    Citations
    Viereckel, T., Dumas, S., Smith-Anttila, C. J. A., Vlcek, B., Bimpisidis, Z., Lagerström, M. C., Konradsson-Geuken, Å. & Wallén-Mackenzie, Å. (2016). Midbrain Gene Screening Identifies a New Mesoaccumbal Glutamatergic Pathway and a Marker for Dopamine Cells Neuroprotected in Parkinson's Disease.. Sci Rep, 6 (1), pp.35203-. https://doi.org/10.1038/srep35203.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/260459
    DOI
    10.1038/srep35203
    Open Access at PMC
    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5071886
    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.

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