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

Chihiro Hisatsune, Yukiko Kuroda, Takumi Akagi, Takashi Torashima, Hirokazu Hirai, Tsutomu Hashikawa, Takafumi Inoue, Katsuhiko Mikoshiba

Research output: Contribution to journalArticle

45 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)10916-10924
Number of pages9
JournalJournal of Neuroscience
Volume26
Issue number42
DOIs
Publication statusPublished - 2006 Oct 18

Keywords

  • BDNF
  • Ca release
  • Dendrite outgrowth
  • Granule cell
  • IP receptor
  • Purkinje cell

ASJC Scopus subject areas

  • Neuroscience(all)

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