NMDA Receptor GluN2B (GluRε2/NR2B) Subunit Is Crucial for Channel Function, Postsynaptic Macromolecular Organization, and Actin Cytoskeleton at Hippocampal CA3 Synapses

Akashi, Kaori; Kakizaki, Toshikazu; Kamiya, Haruyuki et al.

The Journal of Neuroscience, 2009, 29(35), 10869-10882

Permalink : https://hdl.handle.net/2115/39397

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アクセス権
open access
URI
https://hdl.handle.net/2115/39397
タイトル
NMDA Receptor GluN2B (GluRε2/NR2B) Subunit Is Crucial for Channel Function, Postsynaptic Macromolecular Organization, and Actin Cytoskeleton at Hippocampal CA3 Synapses
著者
Akashi, Kaori ; Kakizaki, Toshikazu ; Kamiya, Haruyuki ; Fukaya, Masahiro ; Yamasaki, Miwako ; Abe, Manabu ; Natsume, Rie ; Watanabe, Masahiko ; Sakimura, Kenji
著者名
Akashi, Kaori
著者名
Kakizaki, Toshikazu
著者名
Kamiya, Haruyuki
著者名
Fukaya, Masahiro
著者名
Yamasaki, Miwako
著者名
Abe, Manabu
著者名
Natsume, Rie
e-Rad_Researcher
70210945
著者名
Watanabe, Masahiko
著者名
Sakimura, Kenji
言語
英語
発行日
2009-09-02
出版者
Society for Neuroscience
収録物名
The Journal of Neuroscience
巻(号)
29(35)
ページ
10869-10882
抄録
GluN2B (GluRε2/NR2B) subunit is involved in synapse development, synaptic plasticity, and cognitive function. However, its roles in synaptic expression and function of NMDA receptors (NMDARs) in the brain remain mostly unknown because of the neonatal lethality of global knock-out mice. To address this, we generated conditional knock-out mice, in which GluN2B was ablated exclusively in hippocampal CA3 pyramidal cells. By immunohistochemistry, GluN2B disappeared and GluN1 (GluRζ1/NR1) was moderately reduced, whereas GluN2A (GluRε1/NR2A) and postsynaptic density-95 (PSD-95) were unaltered in the mutant CA3. This was consistent with protein contents in the CA3 crude fraction: 9.6% of control level for GluN2B, 47.7% for GluN1, 90.6% for GluN2A, and 98.0% for PSD-95. Despite the remaining NMDARs, NMDAR-mediated currents and long-term potentiation were virtually lost at various CA3 synapses. Then, we compared synaptic NMDARs by postembedding immunogold electron microscopy and immunoblot using the PSD fraction. In the mutant CA3, GluN1 was severely reduced in both immunogold (20.6-23.6%) and immunoblot (24.6%), whereas GluN2A and PSD-95 were unchanged in immunogold but markedly reduced in the PSD fraction (51.4 and 36.5%, respectively), indicating increased detergent solubility of PSD molecules. No such increased solubility was observed for GluN2B in the CA3 of GluN2A-knock-out mice. Furthermore, significant decreases were found in the ratio of filamentous to globular actin (49.5%) and in the density of dendritic spines (76.2%). These findings suggest that GluN2B is critically involved in NMDAR channel function, organization of postsynaptic macromolecular complexes, formation or maintenance of dendritic spines, and regulation of the actin cytoskeleton.
資源タイプ
学術雑誌論文
出版タイプ
Version of Record
権利情報
Copyright©2009 Society for Neuroscience
PISSN
0270-6474
関連情報 (isIdenticalTo)
出版社版DOI
https://doi.org/10.1523/JNEUROSCI.5531-08.2009