NMDA receptors control development of somatosensory callosal axonal projections.
NMDA receptors control development of somatosensory callosal axonal projections.
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DOI：
10.7554/elife.59612
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发表时间：
2021-03-04
期刊：
影响因子：
7.7
通讯作者：
Pleasure SJ
中科院分区：
文献类型：
--
作者：
Zhou J;Lin Y;Huynh T;Noguchi H;Bush JO;Pleasure SJ
初级躯体感觉皮层（S1）的胼胝体投射是处理躯体感觉输入和整合感觉-运动信息的关键。S1的胼胝体神经支配模式是如何在出生后早期发育过程中形成的尚不清楚。我们发现这些胼胝体投射的正常终止模式在皮质特异性NMDAR突变体中被破坏。而不是选择性地投射到初级/次级体感皮层（S1/S2）的边界，轴突均匀分布在整个S1。此外，这种投射的密度随着出生后的生活而增加，直到小鼠在P30死亡。通过结合遗传和抗体介导的功能丧失，我们证明了靶S1中含有GluN2B的NMDA受体介导了这种指导表型，从而在半球间连接中发挥了核心作用。此外，我们还发现，NMDA受体在胼胝体回路形成中的这种功能不依赖于离子通道功能，而是与EPHRIN-B/EPHB系统一起起作用。因此，在靶S1皮层的NMDAR调节胼胝体回路的形成可能是通过调节EPH依赖的排斥。
Callosal projections from primary somatosensory cortex (S1) are key for processing somatosensory inputs and integrating sensory-motor information. How the callosal innervation pattern in S1 is formed during early postnatal development is not clear. We found that the normal termination pattern of these callosal projections is disrupted in cortex specific NMDAR mutants. Rather than projecting selectively to the primary/secondary somatosensory cortex (S1/S2) border, axons were uniformly distributed throughout S1. In addition, the density of this projection increased over postnatal life until the mice died by P30. By combining genetic and antibody-mediated loss of function, we demonstrated that it is GluN2B-containing NMDA receptors in target S1 that mediate this guidance phenotype, thus playing a central role in interhemispheric connectivity. Furthermore, we found that this function of NMDA receptors in callosal circuit formation is independent of ion channel function and works with the EPHRIN-B/EPHB system. Thus, NMDAR in target S1 cortex regulates the formation callosal circuits perhaps by modulating EPH-dependent repulsion.