title: Pallidothalamic-projecting neurons in Macaca fascicularis co-express GABAergic and glutamatergic markers as seen in control, MPTP-treated and dyskinetic monkeys.
abstract: GABAergic neurons within the internal division of the globus pallidus (GPi) are the main source of basal ganglia output reaching the thalamic ventral nuclei in monkeys. Following dopaminergic denervation, pallidothalamic-projecting neurons are known to be hyperactive, whereas a reduction in GPi activity is typically observed in lesioned animals showing levodopa-induced dyskinesia. Besides the mRNAs coding for GABAergic markers (GAD65 and GAD67), we show that all GPi neurons innervating thalamic targets also express transcripts for the isoforms 1 and 2 of the vesicular glutamate transporter (vGlut1 and vGlut2 mRNA). Indeed, dual immunofluorescent detection of GAD67 and vGlut1/2 confirmed the data gathered from in situ hybridization experiments, therefore demonstrating that the detected mRNAs are translated into the related proteins. Furthermore, the dopaminergic lesion resulted in an up-regulation of expression levels for both GAD65 and GAD67 mRNA within identified pallidothalamic-projecting neurons. This was coupled with a down-regulation of GAD65/67 mRNA expression levels in GPi neurons innervating thalamic targets in monkeys showing levodopa-induced dyskinesia. By contrast, the patterns of gene expression for both vGlut1 and vGlut2 mRNAs remained unchanged across GPi projection neurons in control, MPTP-treated and dyskinetic monkeys. In summary, both GABAergic and glutamatergic markers were co-expressed by GPi efferent neurons in primates. Although the status of the dopaminergic system directly modulates the expression levels of GAD65/67 mRNA, the observed expression of vGlut1/2 mRNA is not regulated by either dopaminergic removal or by continuous stimulation with dopaminergic agonists.
authors.affiliation: Neurosciences Division, Center for Applied Medical Research (CIMA & CIBERNED), Pio XII Ave 55, Edificio CIMA, 31008 Pamplona, Spain.
authors.forename: Lorena
authors.initials: L
authors.lastname: Conte-Perales
authors.forename: Alberto J
authors.initials: AJ
authors.lastname: Rico
authors.forename: Pedro
authors.initials: P
authors.lastname: Barroso-Chinea
authors.forename: Virginia
authors.initials: V
authors.lastname: Gómez-Bautista
authors.forename: Elvira
authors.initials: E
authors.lastname: Roda
authors.forename: Natasha
authors.initials: N
authors.lastname: Luquin
authors.forename: Salvador
authors.initials: S
authors.lastname: Sierra
authors.forename: José L
authors.initials: JL
authors.lastname: Lanciego
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D003124:Colorimetry; D017931:DNA Primers / Q000235:genetics; D004298:Dopamine / Q000172:deficiency*; D004409:Dyskinesia, Drug-Induced / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D059330:GABAergic Neurons / Q000378:metabolism*; D005917:Globus Pallidus / Q000166:cytology* / Q000502:physiology; D005968:Glutamate Decarboxylase / Q000378:metabolism; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D017404:In Situ Hybridization, Fluorescence; D007980:Levodopa / Q000633:toxicity; D008252:Macaca fascicularis; D008297:Male; D009476:Neurons, Efferent / Q000378:metabolism*; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000188:drug therapy*; D016133:Polymerase Chain Reaction; D018709:Statistics, Nonparametric; D013788:Thalamus / Q000502:physiology; D050598:Vesicular Glutamate Transport Protein 1 / Q000378:metabolism
chemical_list: D017931:DNA Primers; D050598:Vesicular Glutamate Transport Protein 1; D007980:Levodopa; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1; C401141:glutamate decarboxylase 2; D004298:Dopamine