title: Glutamatergic and cholinergic pedunculopontine neurons innervate the thalamic parafascicular nucleus in rats: changes following experimental parkinsonism.
abstract: The tegmental pedunculopontine nucleus (PPN) is a basal ganglia-related structure that has recently gained renewed interest as a potential surgical target for the treatment of several aspects of Parkinson's disease. However, the underlying anatomical substrates sustaining the choice of the PPN nucleus as a surgical candidate remain poorly understood. Here, we characterized the chemical phenotypes of different subtypes of PPN efferent neurons innervating the rat parafascicular (PF) nucleus. Emphasis was placed on elucidating the impact of unilateral nigrostriatal denervation on the expression patterns of the mRNA coding the vesicular glutamate transporter type 2 (vGlut2 mRNA). We found a bilateral projection from the PPN nucleus to the PF nucleus arising from cholinergic and glutamatergic efferent neurons, with a small fraction of projection neurons co-expressing both cholinergic and glutamatergic markers. Furthermore, the unilateral nigrostriatal depletion induced a bilateral twofold increase in the expression levels of vGlut2 mRNA within the PPN nucleus. Our results support the view that heterogeneous chemical profiles account for PPN efferent neurons innervating thalamic targets. Moreover, a bilateral enhancement of glutamatergic transmission arising from the PPN nucleus occurs following unilateral dopaminergic denervation, therefore sustaining the well-known hyperactivity of the PF nucleus in parkinsonian-like conditions. In conclusion, our data suggest that the ascending projections from the PPN that reach basal ganglia-related targets could play an important role in the pathophysiology of Parkinson's disease.
authors.affiliation: Neurosciences Division, Center for Applied Medical Research (CIMA and CIBERNED), University of Navarra, Pio XII Ave 55, Edificio CIMA, 31008 Pamplona, Spain.
authors.forename: Pedro
authors.initials: P
authors.lastname: Barroso-Chinea
authors.forename: Alberto J
authors.initials: AJ
authors.lastname: Rico
authors.forename: Lorena
authors.initials: L
authors.lastname: Conte-Perales
authors.forename: Virginia
authors.initials: V
authors.lastname: Gómez-Bautista
authors.forename: Natasha
authors.initials: N
authors.lastname: Luquin
authors.forename: Salvador
authors.initials: S
authors.lastname: Sierra
authors.forename: Elvira
authors.initials: E
authors.lastname: Roda
authors.forename: José L
authors.initials: JL
authors.lastname: Lanciego
mesh_terms: D000818:Animals; D059329:Cholinergic Neurons / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D018698:Glutamic Acid / Q000378:metabolism; D006652:Histological Techniques; D007124:Immunoenzyme Techniques; D017404:In Situ Hybridization, Fluorescence; D020646:Intralaminar Thalamic Nuclei / Q000166:cytology*; D042282:Microdissection; D009476:Neurons, Efferent / Q000378:metabolism*; D020734:Parkinsonian Disorders / Q000503:physiopathology*; D045042:Pedunculopontine Tegmental Nucleus / Q000166:cytology*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D013266:Stilbamidines; D050599:Vesicular Glutamate Transport Protein 2 / Q000378:metabolism*
chemical_list: C049774:2-hydroxy-4,4'-diamidinostilbene, methanesulfonate salt; D017931:DNA Primers; D012333:RNA, Messenger; C493475:Slc17a6 protein, rat; D013266:Stilbamidines; D050599:Vesicular Glutamate Transport Protein 2; D018698:Glutamic Acid