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Cbln1 accumulates and colocalizes with Cbln3 and GluRδ2 at parallel fiber–Purkinje cell synapses in the mouse cerebellum
Author(s) -
Miura Eriko,
Matsuda Keiko,
Morgan James I.,
Yuzaki Michisuke,
Watanabe Masahiko
Publication year - 2009
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.2009.06632.x
Subject(s) - parallel fiber , cerebellum , purkinje cell , granule cell , microbiology and biotechnology , glutamate receptor , synaptic plasticity , biology , mossy fiber (hippocampus) , chemistry , neuroscience , receptor , biochemistry , central nervous system , dentate gyrus
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.