The glutamate receptor GluN2 subunit regulates synaptic trafficking of AMPA receptors in the neonatal mouse brain
| Autor: | Kazuki Nakao, Miwako Yamasaki, Atsu Aiba, Ayako M. Watabe, Toshiya Manabe, Itone Ogawa, Shun Hamada, Yuji Kiyama, Hidetoshi Kassai, Masahiko Watanabe |
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| Rok vydání: | 2014 |
| Předmět: |
musculoskeletal
neural and ocular physiology General Neuroscience Glutamate receptor Brain AMPA receptor Biology Receptors N-Methyl-D-Aspartate Mice Protein Transport Synaptic fatigue nervous system Animals Newborn Synaptic augmentation Synaptic plasticity NMDA receptor Animals Gene Knock-In Techniques Receptors AMPA Receptor Postsynaptic density Neuroscience |
| Zdroj: | The European journal of neuroscience. 40(8) |
| ISSN: | 1460-9568 |
| Popis: | The N-methyl-d-aspartate receptor (NMDAR) plays various physiological and pathological roles in neural development, synaptic plasticity and neuronal cell death. It is composed of two GluN1 and two GluN2 subunits and, in the neonatal hippocampus, most synaptic NMDARs are GluN2B-containing receptors, which are gradually replaced with GluN2A-containing receptors during development. Here, we examined whether GluN2A could be substituted for GluN2B in neural development and functions by analysing knock-in (KI) mice in which GluN2B is replaced with GluN2A. The KI mutation was neonatally lethal, although GluN2A-containing receptors were transported to the postsynaptic membrane even without GluN2B and functional at synapses of acute hippocampal slices of postnatal day 0, indicating that GluN2A-containing NMDARs could not be substituted for GluN2B-containing NMDARs. Importantly, the synaptic α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) subunit GluA1 was increased, and the transmembrane AMPAR regulatory protein, which is involved in AMPAR synaptic trafficking, was increased in KI mice. Although the regulation of AMPARs by GluN2B has been reported in cultured neurons, we showed here that AMPAR-mediated synaptic responses were increased in acute KI slices, suggesting differential roles of GluN2A and GluN2B in AMPAR expression and trafficking in vivo. Taken together, our results suggest that GluN2B is essential for the survival of animals, and that the GluN2B–GluN2A switching plays a critical role in synaptic integration of AMPARs through regulation of GluA1 in the whole animal. |
| Databáze: | OpenAIRE |
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