Cbln1 accumulates and colocalizes with Cbln3 and GluRδ2 at parallel fiber-Purkinje cell synapses in the mouse cerebellum

Eriko Miura, Keiko Matsuda, James I. Morgan, Michisuke Yuzaki, Masahiko Watanabe

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Cbln1 (a.k.a. precerebellin) is secreted from cerebellar granule cells as homohexamer or in heteromeric complexes with Cbln3. Cbln1 plays crucial roles in regulating morphological integrity of parallel fiber (PF)-Purkinje cell (PC) synapses and synaptic plasticity. Cbln1-knockout mice display severe cerebellar phenotypes that are essentially indistinguishable from those in glutamate receptor GluRδ2-null mice, and include severe reduction in the number of PF-PC synapses and loss of long-term depression of synaptic transmission. To understand better the relationship between Cbln1, Cbln3 and GluRδ2, we performed light and electron microscopic immunohistochemical analyses using highly specific antibodies and antigen-exposing methods, i.e. pepsin pretreatment for light microscopy and postembedding immunogold for electron microscopy. In conventional immunohistochemistry, Cbln1 was preferentially associated with non-terminal portions of PF axons in the molecular layer but rarely overlapped with Cbln3. In contrast, antigen-exposing methods not only greatly intensified Cbln1 immunoreactivity in the molecular layer, but also revealed its high accumulation in the synaptic cleft of PF-PC synapses. No such synaptic accumulation was evident at other PC synapses. Furthermore, Cbln1 now came to overlap almost completely with Cbln3 and GluRδ2 at PF-PC synapses. Therefore, the convergence of all three molecules provides the anatomical basis for a common signaling pathway regulating circuit development and synaptic plasticity in the cerebellum.

Original languageEnglish
Pages (from-to)693-706
Number of pages14
JournalEuropean Journal of Neuroscience
Volume29
Issue number4
DOIs
Publication statusPublished - 2009 Feb

Fingerprint

Purkinje Cells
Synapses
Cerebellum
Neuronal Plasticity
Light
Antigens
Pepsin A
Glutamate Receptors
Knockout Mice
Synaptic Transmission
Axons
Microscopy
Electron Microscopy
Immunohistochemistry
Electrons
Phenotype
Antibodies

Keywords

  • Cbln
  • GluRδ2
  • Immunohistochemistry
  • Mouse
  • Parallel fiber
  • Purkinje cell

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Cbln1 accumulates and colocalizes with Cbln3 and GluRδ2 at parallel fiber-Purkinje cell synapses in the mouse cerebellum. / Miura, Eriko; Matsuda, Keiko; Morgan, James I.; Yuzaki, Michisuke; Watanabe, Masahiko.

In: European Journal of Neuroscience, Vol. 29, No. 4, 02.2009, p. 693-706.

Research output: Contribution to journalArticle

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