title: Cellular and behavioral outcomes of dorsal striatonigral neuron ablation: new insights into striatal functions.
abstract: The striatum is the input structure of the basal ganglia network that contains heterogeneous neuronal populations, including two populations of projecting neurons called the medium spiny neurons (MSNs), and different types of interneurons. We developed a transgenic mouse model enabling inducible ablation of the striatonigral MSNs constituting the direct pathway by expressing the human diphtheria toxin (DT) receptor under the control of the Slc35d3 gene promoter, a gene enriched in striatonigral MSNs. DT injection into the striatum triggered selective elimination of the majority of striatonigral MSNs. DT-mediated ablation of striatonigral MSNs caused selective loss of cholinergic interneurons in the dorsal striatum but not in the ventral striatum (nucleus accumbens), suggesting a region-specific critical role of the direct pathway in striatal cholinergic neuron homeostasis. Mice with DT injection into the dorsal striatum showed altered basal and cocaine-induced locomotion and dramatic reduction of L-DOPA-induced dyskinesia in the parkinsonian condition. In addition, these mice exhibited reduced anxiety, revealing a role of the dorsal striatum in the modulation of behaviors involving an emotional component, behaviors generally associated with limbic structures. Altogether, these results highlight the implication of the direct striatonigral pathway in the regulation of heterogeneous functions from cell survival to regulation of motor and emotion-associated behaviors.
authors.affiliation: Institut de Biologie du Développement de Marseille (IBDM), Aix-Marseille University (AMU), Centre National de la Recherche Scientifique (CNRS), UMR 7288, Marseille Cedex 9, France.
authors.forename: Delphine
authors.initials: D
authors.lastname: Révy
authors.affiliation: Institut de Biologie du Développement de Marseille (IBDM), Aix-Marseille University (AMU), Centre National de la Recherche Scientifique (CNRS), UMR 7288, Marseille Cedex 9, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Jaouen
authors.affiliation: Institut de Biologie du Développement de Marseille (IBDM), Aix-Marseille University (AMU), Centre National de la Recherche Scientifique (CNRS), UMR 7288, Marseille Cedex 9, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Salin
authors.affiliation: Institut de Biologie du Développement de Marseille (IBDM), Aix-Marseille University (AMU), Centre National de la Recherche Scientifique (CNRS), UMR 7288, Marseille Cedex 9, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Melon
authors.affiliation: Institut de Biologie du Développement de Marseille (IBDM), Aix-Marseille University (AMU), Centre National de la Recherche Scientifique (CNRS), UMR 7288, Marseille Cedex 9, France.
authors.forename: Dorian
authors.initials: D
authors.lastname: Chabbert
authors.affiliation: The European Brain Research Institute, Roma, Italy.
authors.forename: Elisiana
authors.initials: E
authors.lastname: Tafi
authors.affiliation: The European Brain Research Institute, Roma, Italy.
authors.forename: Lena
authors.initials: L
authors.lastname: Concetta
authors.affiliation: Institut Pasteur, Mouse Genetics Engineering Center, Paris Cedex 15, France.
authors.forename: Francina
authors.initials: F
authors.lastname: Langa
authors.affiliation: Laboratoire de Neurosciences Cognitives, Aix-Marseille University, Centre National de la Recherche Scientifique (CNRS), UMR 7291, Marseille Cedex 3, France.
authors.forename: Marianne
authors.initials: M
authors.lastname: Amalric
authors.affiliation: Institut de Biologie du Développement de Marseille (IBDM), Aix-Marseille University (AMU), Centre National de la Recherche Scientifique (CNRS), UMR 7288, Marseille Cedex 9, France.
authors.forename: Lydia
authors.initials: L
authors.lastname: Kerkerian-Le Goff
authors.affiliation: The European Brain Research Institute, Roma, Italy.
authors.forename: Hélène
authors.initials: H
authors.lastname: Marie
authors.affiliation: Institut de Biologie du Développement de Marseille (IBDM), Aix-Marseille University (AMU), Centre National de la Recherche Scientifique (CNRS), UMR 7288, Marseille Cedex 9, France.
authors.forename: Corinne
authors.initials: C
authors.lastname: Beurrier
mesh_terms: D000818:Animals; D000978:Antiparkinson Agents / Q000633:toxicity; D001007:Anxiety / Q000503:physiopathology*; D059329:Cholinergic Neurons / Q000187:drug effects / Q000502:physiology*; D003042:Cocaine / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects / Q000502:physiology*; D004167:Diphtheria Toxin / Q000633:toxicity; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D004409:Dyskinesia, Drug-Induced / Q000503:physiopathology; D066257:Heparin-binding EGF-like Growth Factor / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007395:Interneurons / Q000187:drug effects / Q000502:physiology*; D007980:Levodopa / Q000633:toxicity; D008822:Mice, Transgenic; D009004:Monosaccharide Transport Proteins / Q000235:genetics; D009068:Movement / Q000187:drug effects / Q000502:physiology*; D009434:Neural Pathways / Q000187:drug effects / Q000502:physiology; D009498:Neurotoxins / Q000633:toxicity; D011401:Promoter Regions, Genetic; D013378:Substantia Nigra / Q000187:drug effects / Q000502:physiology*
chemical_list: D000978:Antiparkinson Agents; D004167:Diphtheria Toxin; D018765:Dopamine Uptake Inhibitors; D066257:Heparin-binding EGF-like Growth Factor; D009004:Monosaccharide Transport Proteins; D009498:Neurotoxins; C518133:Slc35d3 protein, mouse; D007980:Levodopa; D003042:Cocaine