title: Inositol 1,4,5-trisphosphate receptor type 1 in granule cells, not in Purkinje cells, regulates the dendritic morphology of Purkinje cells through brain-derived neurotrophic factor production.
abstract: Here, we show that cultured Purkinje cells from inositol 1,4,5-trisphosphate receptor type 1 knock-out (IP3R1KO) mice exhibited abnormal dendritic morphology. Interestingly, despite the huge amount of IP3R1 expression in Purkinje cells, IP3R1 in granule cells, not in the Purkinje cells, was responsible for the shape of Purkinje cell dendrites. We also found that BDNF application rescued the dendritic abnormality of IP3R1KO Purkinje cells, and that the increase in BDNF expression in response to activation of AMPA receptor (AMPAR) and metabotropic glutamate receptor (mGluR) was impaired in IP3R1KO cerebellar granule cells. In addition, we observed abnormalities in the dendritic morphology of Purkinje cells and in the ultrastructure of parallel fiber-Purkinje cell (PF-PC) synapses in IP3R1KO mice in vivo. We concluded that activation of AMPAR and mGluR increases BDNF expression through IP3R1-mediated signaling in cerebellar granule cells, which contributes to the dendritic outgrowth of Purkinje cells intercellularly, possibly by modifying PF-PC synaptic efficacy.
authors.affiliation: Laboratory for Developmental Neurobiology, RIKEN Brain Science Institute, Wako City, Saitama 351-0198, Japan. chihiro@ims.u-tokyo.ac.jp
authors.forename: Chihiro
authors.initials: C
authors.lastname: Hisatsune
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Kuroda
authors.forename: Takumi
authors.initials: T
authors.lastname: Akagi
authors.forename: Takashi
authors.initials: T
authors.lastname: Torashima
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Hirai
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Hashikawa
authors.forename: Takafumi
authors.initials: T
authors.lastname: Inoue
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Mikoshiba
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D015220:Calcium Channels / Q000172:deficiency / Q000502:physiology*; D002478:Cells, Cultured; D003712:Dendrites / Q000235:genetics / Q000378:metabolism*; D053496:Inositol 1,4,5-Trisphosphate Receptors; D051379:Mice; D018345:Mice, Knockout; D011689:Purkinje Cells / Q000166:cytology* / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000172:deficiency / Q000502:physiology*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D015220:Calcium Channels; D053496:Inositol 1,4,5-Trisphosphate Receptors; D018160:Receptors, Cytoplasmic and Nuclear