title: Regulation of striatal dopamine responsiveness by Notch/RBP-J signaling.
abstract: Dopamine signaling is essential for reward learning and fear-related learning, and thought to be involved in neuropsychiatric diseases. However, the molecular mechanisms underlying the regulation of dopamine responsiveness is unclear. Here we show the critical roles of Notch/RBP-J signaling in the regulation of dopamine responsiveness in the striatum. Notch/RBP-J signaling regulates various neural cell fate specification, and neuronal functions in the adult central nervous system. Conditional deletion of RBP-J specifically in neuronal cells causes enhanced response to apomorphine, a non-selective dopamine agonist, and SKF38393, a D1 agonist, and impaired dopamine-dependent instrumental avoidance learning, which is corrected by SCH23390, a D1 antagonist. RBP-J deficiency drastically reduced dopamine release in the striatum and caused a subtle decrease in the number of dopaminergic neurons. Lentivirus-mediated gene transfer experiments showed that RBP-J deficiency in the striatum was sufficient for these deficits. These findings demonstrated that Notch/RBP-J signaling regulates dopamine responsiveness in the striatum, which may explain the mechanism whereby Notch/RBP-J signaling affects an individual's susceptibility to neuropsychiatric disease.
authors.affiliation: Research Institute, Shiga Medical Center, Shiga, Japan.|Department of Psychiatry, Nara Medical University, Faculty of Medicine, Nara, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Toritsuka
authors.affiliation: Research Institute, Shiga Medical Center, Shiga, Japan.|Department of Psychiatry, Nara Medical University, Faculty of Medicine, Nara, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Kimoto
authors.affiliation: Research Institute, Shiga Medical Center, Shiga, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Muraki
authors.affiliation: Department of Molecular and Tumor Pathology, Chiba University, Graduate School of Medicine, Chiba, Japan.
authors.forename: M
authors.identifier: 0000-0003-1036-840X
authors.initials: M
authors.lastname: Kitagawa
authors.affiliation: Department of Psychiatry, Nara Medical University, Faculty of Medicine, Nara, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Kishimoto
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, School of Medicine, Baltimore, MD, USA.
authors.forename: A
authors.initials: A
authors.lastname: Sawa
authors.affiliation: Research Institute, Shiga Medical Center, Shiga, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Tanigaki
mesh_terms: D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001552:Benzazepines / Q000494:pharmacology; D002452:Cell Count; D004298:Dopamine / Q000378:metabolism*; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D059290:Dopaminergic Neurons / Q000187:drug effects; D018014:Gene Transfer Techniques; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D017447:Receptors, Dopamine D1 / Q000819:agonists / Q000037:antagonists & inhibitors; D051880:Receptors, Notch / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D001552:Benzazepines; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; C583261:Drd1 protein, mouse; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein; C497571:Rbpj protein, mouse; D017447:Receptors, Dopamine D1; D051880:Receptors, Notch; C534628:SCH 23390; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D001058:Apomorphine; D004298:Dopamine