Opposing Role of NMDA Receptor GluN2B and GluN2D in Somatosensory Development and Maturation
Opposing Role of NMDA Receptor GluN2B and GluN2D in Somatosensory Development and Maturation
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DOI：
10.1523/jneurosci.1811-14.2014
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发表时间：
2014-08
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影响因子：
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通讯作者：
Miwako Yamasaki;Rieko Okada;C. Takasaki;Shima Toki;M. Fukaya;R. Natsume;K. Sakimura;M. Mishina
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文献类型：
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作者：
Miwako Yamasaki;Rieko Okada;C. Takasaki;Shima Toki;M. Fukaya;R. Natsume;K. Sakimura;M. Mishina
外周受体和中枢体感站之间正确的地形连接的发展需要活动依赖性突触细化，其中NMDA型谷氨酸受体起着关键作用。在此，我们比较了新生儿NMDA受体的两个主要调节亚基GluN 2B（GluRε2或NR 2B）和GluN 2D（GluRε4或NR 2D）在三叉神经中继站胡须相关图案形成中的功能作用。与同窝对照组相比，通过单侧眶下神经切断评估的胡须相关图案的出现和关键期的终止在GluN 2B +/−小鼠的躯体感觉皮层中延迟了近一天，但在GluN 2D −/−小鼠中提前了近一天。在GluN 2B +/−和GluN 2D −/−小鼠的丘脑和脑干的皮质下中继站也发现了类似的时间转移。相比之下，病变引起的关键期可塑性在躯体感觉皮层，作为评估后行C晶须去除的幅度，是正常的两个突变体。因此，GluN 2B和GluN 2D发挥反作用的时间发展和成熟的躯体感觉地图，而不影响关键期可塑性的大小。为了了解相反的行动，我们然后检查了神经元和突触表达的两个亚基沿着三叉神经通路。在每个三叉神经站，GluN 2B在非GABA能神经元的不对称突触中占优势，而GluN 2D对GABA能神经元的不对称突触具有选择性。总之，我们的研究结果表明，GluN 2B表达在谷氨酸能投射神经元上的谷氨酸能突触直接促进上行通路突触的细化，而GluN 2D表达在GABA能中间神经元上的谷氨酸能突触间接延迟。
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 (GluRε2 or NR2B) and GluN2D (GluRε4 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.