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Opposing Role of NMDA Receptor GluN2B and GluN2D in Somatosensory Development and Maturation

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Title: Opposing Role of NMDA Receptor GluN2B and GluN2D in Somatosensory Development and Maturation
Authors: Yamasaki, Miwako Browse this author →KAKEN DB
Okada, Rieko Browse this author
Takasaki, Chihiro Browse this author →KAKEN DB
Toki, Shima Browse this author →KAKEN DB
Fukaya, Masahiro Browse this author →KAKEN DB
Natsume, Rie Browse this author →KAKEN DB
Sakimura, Kenji Browse this author →KAKEN DB
Mishina, Masayoshi Browse this author →KAKEN DB
Shirakawa, Tetsuo Browse this author →KAKEN DB
Watanabe, Masahiko Browse this author →KAKEN DB
Keywords: barrel
critical period
NMDA receptor
Issue Date: 27-Aug-2014
Publisher: Society for Neuroscience
Journal Title: Journal of Neuroscience
Volume: 34
Issue: 35
Start Page: 11534
End Page: 11548
Publisher DOI: 10.1523/JNEUROSCI.1811-14.2014
PMID: 25164652
Abstract: Development of correct topographical connections between peripheral receptors and central somatosensory stations requires activity-dependent synapse refinement, in which the NMDA type of glutamate receptors plays a key role. Here we compared functional roles of GluN2B (GluR epsilon 2 or NR2B) and GluN2D (GluR epsilon 4 or NR2D), two major regulatory subunits of neonatal NMDA receptors, in development of whisker-related patterning at trigeminal relay stations. Compared with control littermates, both the appearance of whisker-related patterning and the termination of the critical period, as assessed by unilateral infraorbital nerve transection, were delayed by nearly a day in the somatosensory cortex of GluN2B(+/-) mice but advanced by nearly a day in GluN2D(-/-) mice. Similar temporal shifts were found at subcortical relay stations in the thalamus and brainstem of GluN2B(+/-) and GluN2D(-/-) mice. In comparison, the magnitude of lesion-induced critical period plasticity in the somatosensory cortex, as assessed following row-C whisker removal, was normal in both mutants. Thus, GluN2B and GluN2D play counteractive roles in temporal development and maturation of somatosensory maps without affecting the magnitude of critical period plasticity. To understand the opposing action, we then examined neuronal and synaptic expressions of the two subunits along the trigeminal pathway. At each trigeminal station, GluN2B was predominant at asymmetrical synapses of non-GABAergic neurons, whereas GluN2D was selective to asymmetrical synapses of GABAergic neurons. Together, our findings suggest that GluN2B expressed at glutamatergic synapses on glutamatergic projection neurons facilitates refinement of ascending pathway synapses directly, whereas GluN2D expressed at glutamatergic synapses on GABAergic interneurons delays it indirectly.
Type: article
Appears in Collections:医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 渡邉 雅彦

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