title: Protocadherin 17 regulates presynaptic assembly in topographic corticobasal Ganglia circuits.
abstract: Highly topographic organization of neural circuits exists for the regulation of various brain functions in corticobasal ganglia circuits. Although neural circuit-specific refinement during synapse development is essential for the execution of particular neural functions, the molecular and cellular mechanisms for synapse refinement are largely unknown. Here, we show that protocadherin 17 (PCDH17), one of the nonclustered δ2-protocadherin family members, is enriched along corticobasal ganglia synapses in a zone-specific manner during synaptogenesis and regulates presynaptic assembly in these synapses. PCDH17 deficiency in mice causes facilitated presynaptic vesicle accumulation and enhanced synaptic transmission efficacy in corticobasal ganglia circuits. Furthermore, PCDH17(-/-) mice exhibit antidepressant-like phenotypes that are known to be regulated by corticobasal ganglia circuits. Our findings demonstrate a critical role for PCDH17 in the synaptic development of specific corticobasal ganglia circuits and suggest the involvement of PCDH17 in such circuits in depressive behaviors.
authors.affiliation: Division of Oncology, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
authors.forename: Naosuke
authors.initials: N
authors.lastname: Hoshina
authors.forename: Asami
authors.initials: A
authors.lastname: Tanimura
authors.forename: Miwako
authors.initials: M
authors.lastname: Yamasaki
authors.forename: Takeshi
authors.initials: T
authors.lastname: Inoue
authors.forename: Ryoji
authors.initials: R
authors.lastname: Fukabori
authors.forename: Teiko
authors.initials: T
authors.lastname: Kuroda
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Yokoyama
authors.forename: Tohru
authors.initials: T
authors.lastname: Tezuka
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sagara
authors.forename: Shinji
authors.initials: S
authors.lastname: Hirano
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kiyonari
authors.forename: Masahiko
authors.initials: M
authors.lastname: Takada
authors.forename: Kazuto
authors.initials: K
authors.lastname: Kobayashi
authors.forename: Masahiko
authors.initials: M
authors.lastname: Watanabe
authors.forename: Masanobu
authors.initials: M
authors.lastname: Kano
authors.forename: Takanobu
authors.initials: T
authors.lastname: Nakazawa
authors.forename: Tadashi
authors.initials: T
authors.lastname: Yamamoto
mesh_terms: D000161:Acoustic Stimulation; D000818:Animals; D000831:Animals, Newborn; D001479:Basal Ganglia / Q000166:cytology*; D015820:Cadherins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002461:Cell Line, Transformed; D002540:Cerebral Cortex / Q000166:cytology*; D003213:Conditioning, Psychological / Q000502:physiology; D006224:Cricetinae; D003412:Cricetulus; D000076122:Disks Large Homolog 4 Protein; D005106:Exploratory Behavior; D005239:Fear / Q000502:physiology; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D051528:Guanylate Kinases / Q000378:metabolism; D019417:Hindlimb Suspension / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D008253:Macaca mulatta; D008297:Male; D018782:Maze Learning / Q000502:physiology; D008564:Membrane Potentials / Q000235:genetics; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D008854:Microscopy, Electron; D009415:Nerve Net / Q000502:physiology; D009474:Neurons / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D018408:Patch-Clamp Techniques; D017729:Presynaptic Terminals / Q000502:physiology*; D000091363:Protocadherins; D013550:Swimming / Q000502:physiology; D013569:Synapses / Q000235:genetics* / Q000378:metabolism / Q000648:ultrastructure; D009435:Synaptic Transmission / Q000235:genetics; D013572:Synaptic Vesicles / Q000378:metabolism / Q000648:ultrastructure; D050496:Vesicular Glutamate Transport Proteins / Q000378:metabolism
chemical_list: D015820:Cadherins; D000076122:Disks Large Homolog 4 Protein; C501447:Dlg4 protein, mouse; D008565:Membrane Proteins; C438603:PCDH10 protein, human; C529349:PCDH17 protein, human; D000091363:Protocadherins; D050496:Vesicular Glutamate Transport Proteins; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D051528:Guanylate Kinases