Cortex-restricted disruption of NMDAR1 impairs neuronal patterns in the barrel cortex

Cortex-restricted disruption of NMDAR1 impairs neuronal patterns in the barrel cortex
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DOI:
10.1038/35021059
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发表时间:
2000-08-17
期刊:
影响因子:
64.8
通讯作者:
Itohara, S
Itohara, S
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Iwasato, T;Datwani, A;Itohara, S

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在啮齿动物初级躯体感觉皮层中,口鼻部的触须和窦毛以及爪子上受体密集区的形态在拓扑结构上表现为第IV层颗粒细胞(桶状细胞)和丘脑皮质传入神经末梢的离散模块(1,2)。神经活动,特别是由N - 甲基 - D - 天冬氨酸受体(NMDARs)介导的活动在躯体感觉皮层的模式形成中所起的作用一直是一个有争议的话题(3 - 6)。我们培育出了NMDAR1(NR1)基因缺失仅限于兴奋性皮质神经元的小鼠,在此我们表明,在这些小鼠的脑干和丘脑躯体感觉中继站中,与感觉外周相关的模式正常发育。在躯体感觉皮层中,与大触须相对应的丘脑皮质传入神经形成模式并表现出关键期可塑性,但其模式不如正常小鼠皮层中那样明显。与窦毛和趾相对应的其他丘脑皮质模式大多缺失。即使在丘脑皮质传入神经聚集的部位,也不会形成被称为桶状细胞和桶状边界的细胞聚集体。我们的研究结果表明,皮质NMDARs对于第IV层细胞聚集成桶状细胞以及丘脑皮质模式的完整形成至关重要。
In the rodent primary somatosensory cortex, the configuration of whiskers and sinus hairs on the snout and of receptor-dense zones on the paws is topographically represented as discrete modules of layer IV granule cells (barrels) and thalamocortical afferent terminals(1,2). The role of neural activity, particularly activity mediated by NMDARs (N-methyl-D-aspartate receptors), in patterning of the somatosensory cortex has been a subject of debate(3-6). We have generated mice in which deletion of the NMDAR1 (NR1) gene is restricted to excitatory cortical neurons, and here we show that sensory periphery-related patterns develop normally in the brainstem and thalamic somatosensory relay stations of these mice. In the somatosensory cortex, thalamocortical afferents corresponding to large whiskers form patterns and display critical period plasticity, but their patterning is not as distinct as that seen in the cortex of normal mice. Other thalamocortical patterns corresponding to sinus hairs and digits are mostly absent. The cellular aggregates known as barrels and barrel boundaries do not develop even at sites where thalamocortical afferents cluster. Our findings indicate that cortical NMDARs are essential for the aggregation of layer IV cells into barrels and for development of the full complement of thalamocortical patterns.