title: Dysfunction of ventrolateral striatal dopamine receptor type 2-expressing medium spiny neurons impairs instrumental motivation.
abstract: Impaired motivation is present in a variety of neurological disorders, suggesting that decreased motivation is caused by broad dysfunction of the nervous system across a variety of circuits. Based on evidence that impaired motivation is a major symptom in the early stages of Huntington's disease, when dopamine receptor type 2-expressing striatal medium spiny neurons (D2-MSNs) are particularly affected, we hypothesize that degeneration of these neurons would be a key node regulating motivational status. Using a progressive, time-controllable, diphtheria toxin-mediated cell ablation/dysfunction technique, we find that loss-of-function of D2-MSNs within ventrolateral striatum (VLS) is sufficient to reduce goal-directed behaviours without impairing reward preference or spontaneous behaviour. Moreover, optogenetic inhibition and ablation of VLS D2-MSNs causes, respectively, transient and chronic reductions of goal-directed behaviours. Our data demonstrate that the circuitry containing VLS D2-MSNs control motivated behaviours and that VLS D2-MSN loss-of-function is a possible cause of motivation deficits in neurodegenerative diseases.
authors.affiliation: Department of Neuropsychiatry, Keio University School of Medicine, Tokyo 160-8582, Japan.|Research Fellow of Japan Society for the Promotion of Science (RPD), Tokyo 102-0083, Japan.
authors.forename: Iku
authors.initials: I
authors.lastname: Tsutsui-Kimura
authors.affiliation: Department of Neuropsychiatry, Keio University School of Medicine, Tokyo 160-8582, Japan.|Department of Physiology, Keio University School of Medicine, Tokyo 160-8582, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Takiue
authors.affiliation: Department of Neuropsychiatry, Keio University School of Medicine, Tokyo 160-8582, Japan.
authors.forename: Keitaro
authors.initials: K
authors.lastname: Yoshida
authors.affiliation: Department of Neuropsychiatry, Keio University School of Medicine, Tokyo 160-8582, Japan.
authors.forename: Ming
authors.initials: M
authors.lastname: Xu
authors.affiliation: Department of Neuropsychiatry, Keio University School of Medicine, Tokyo 160-8582, Japan.|Department of Physiology, Keio University School of Medicine, Tokyo 160-8582, Japan.
authors.forename: Ryutaro
authors.initials: R
authors.lastname: Yano
authors.affiliation: Department of Physiology, National Defense Medical College, Saitama 359-8513, Japan.
authors.forename: Hiroyuki
authors.identifier: 0000-0002-1816-7912
authors.initials: H
authors.lastname: Ohta
authors.affiliation: Department of Neuropsychiatry, Keio University School of Medicine, Tokyo 160-8582, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nishida
authors.affiliation: Department of Neuropsychiatry, Keio University School of Medicine, Tokyo 160-8582, Japan.
authors.forename: Youcef
authors.initials: Y
authors.lastname: Bouchekioua
authors.affiliation: Department of Physiology, Keio University School of Medicine, Tokyo 160-8582, Japan.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Okano
authors.affiliation: Department of Anatomy and Embryology, University of Hokkaido, Hokkaido 060-8638, Japan.
authors.forename: Motokazu
authors.initials: M
authors.lastname: Uchigashima
authors.affiliation: Department of Anatomy and Embryology, University of Hokkaido, Hokkaido 060-8638, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Watanabe
authors.affiliation: Department of Neuropsychiatry, Keio University School of Medicine, Tokyo 160-8582, Japan.
authors.forename: Norio
authors.initials: N
authors.lastname: Takata
authors.affiliation: Center for Learning and Memory, Department of Neuroscience, The University of Texas at Austin, Austin, Texas 78712, USA.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Drew
authors.affiliation: Division of System Neurophysiology, National Institute for Physiological Sciences, Okazaki 444-8585, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Sano
authors.affiliation: Department of Neuropsychiatry, Keio University School of Medicine, Tokyo 160-8582, Japan.
authors.forename: Masaru
authors.initials: M
authors.lastname: Mimura
authors.affiliation: Department of Neuropsychiatry, Keio University School of Medicine, Tokyo 160-8582, Japan.
authors.forename: Kenji F
authors.initials: KF
authors.lastname: Tanaka
mesh_terms: D000818:Animals; D003163:Competitive Behavior / Q000502:physiology; D003342:Corpus Striatum / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D059290:Dopaminergic Neurons / Q000378:metabolism* / Q000502:physiology; D055724:Electrophysiological Phenomena; D005260:Female; D006040:Goals; D008297:Male; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D009042:Motivation; D009043:Motor Activity / Q000235:genetics / Q000502:physiology; D017448:Receptors, Dopamine D2 / Q000235:genetics / Q000378:metabolism*
chemical_list: D017448:Receptors, Dopamine D2