Premium
Glycinergic transmission and postsynaptic activation of Ca MKII are required for glycine receptor clustering in vivo
Author(s) -
Yamanaka Iori,
Miki Mariko,
Asakawa Kazuhide,
Kawakami Koichi,
Oda Yoichi,
Hirata Hiromi
Publication year - 2013
Publication title -
genes to cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.912
H-Index - 115
eISSN - 1365-2443
pISSN - 1356-9597
DOI - 10.1111/gtc.12032
Subject(s) - glycine receptor , neurotransmission , strychnine , postsynaptic potential , biology , neuroscience , inhibitory postsynaptic potential , gephyrin , postsynaptic current , neurotransmitter , microbiology and biotechnology , glycine , receptor , excitatory postsynaptic potential , biochemistry , central nervous system , amino acid
Synaptic transmission‐dependent regulation of neurotransmitter receptor accumulation at postsynaptic sites underlies the formation, maintenance and maturation of synaptic function. Previous in vitro studies showed that glycine receptor (GlyR) clustering requires synaptic inputs. However, in vivo GlyR regulation by synaptic transmission is not fully understood. Here, we established a model system using developing zebrafish, in which GlyRs are expressed in Mauthner cells (M‐cells), a pair of giant, reticulospinal, hindbrain neurons, thereby enabling analysis of GlyR clusters over time in identifiable cells. Bath application of a glycinergic blocker, strychnine, to developing zebrafish prevented postsynaptic GlyR cluster formation in the M‐cells. After strychnine removal, the GlyR clusters appeared in the M‐cells. At a later stage, glycinergic transmission blockade impaired maintenance of GlyR clusters. We also found that pharmacological blockade of either L‐type Ca 2+ channels or calcium‐/calmodulin‐dependent protein kinase II (Ca MKII ) disturbed GlyR clustering. In addition, the M‐cell‐specific Ca MKII inactivation using the Gal4‐ UAS system significantly impaired GlyR clustering in the M‐cells. Thus, the formation and maintenance of GlyR clusters in the M‐cells in the developing animals are regulated in a synaptic transmission‐dependent manner, and Ca MKII activation at the postsynapse is essential for GlyR clustering. This is the first demonstration of synaptic transmission‐dependent modulation of synaptic GlyRs in vivo .