Glycinergic transmission and postsynaptic activation of CaMKII are required for glycine receptor clustering in vivo.

Iori Yamanaka, Mariko Miki, Kazuhide Asakawa, Koichi Kawakami, Yoichi Oda, Hiromi Hirata

Division of Biological Science, Graduate School of Science, Nagoya University, Nagoya, 464-8602, Japan.

Genes to cells : devoted to molecular & cellular mechanisms 2013 Mar

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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 (CaMKII) disturbed GlyR clustering. In addition, the M-cell-specific CaMKII 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 CaMKII activation at the postsynapse is essential for GlyR clustering. This is the first demonstration of synaptic transmission-dependent modulation of synaptic GlyRs in vivo. © 2013 The Authors Genes to Cells © 2013 by the Molecular Biology Society of Japan and Wiley Publishing Asia Pty Ltd.

Citation

Iori Yamanaka, Mariko Miki, Kazuhide Asakawa, Koichi Kawakami, Yoichi Oda, Hiromi Hirata. Glycinergic transmission and postsynaptic activation of CaMKII are required for glycine receptor clustering in vivo. Genes to cells : devoted to molecular & cellular mechanisms. 2013 Mar;18(3):211-24