Reelin signaling facilitates maturation of CA1 glutamatergic Synapses
Reelin signaling facilitates maturation of CA1 glutamatergic Synapses
复制标题
DOI：
10.1152/jn.00869.2006
复制
发表时间：
2007-03-01
影响因子：
2.5
通讯作者：
Weeber, Edwin J.
中科院分区：
文献类型：
--
作者：
Qiu, Shenfeng;Weeber, Edwin J.
通过低密度脂蛋白受体家族成员载脂蛋白E受体2（apoER 2）和极低密度脂蛋白受体（VLDLR）的Reelin信号传导在胚胎脑发育期间指示神经元分层中起关键作用。最近的证据表明，这个信号系统也在出生后的大脑中发挥作用，调节突触传递，可塑性和认知行为，很可能是由于与N-甲基-D-天冬氨酸（NMDA）受体的功能耦合。在这项研究中，我们研究了影响reelin对成熟的CA 1神经元功能的电生理和生化方法。在培养的海马脑片中，reelin处理增加AMPAR介导的兴奋性突触后电流的振幅和诱发的AMPA/NMDA受体电流比。此外，reelin处理还减少了沉默突触的数量，促进了NMDARs从NR 2B到NR 2A的发育转换，并增加了CA 1组织中AMPAR的表面表达。在培养的海马神经元从reeler胚胎，减少数量的AMPAR亚基GluR 1和NMDAR亚基NR 1集群观察到与野生型胚胎相比。在reeler文化中补充reelin消除了这些基因型差异。这些结果表明，reelin和脂蛋白受体介导的信号可能在海马神经元功能发育成熟过程中起作用，因此代表了一个潜在的重要机制，控制突触强度和可塑性在出生后海马。
Reelin signaling through the low-density lipoprotein receptor family members, apoliproprotein E receptor 2 (apoER2) and very-low-density lipoprotein receptor (VLDLR), plays a pivotal role in dictating neuronal lamination during embryonic brain development. Recent evidence suggests that this signaling system also plays a role in the postnatal brain to modulate synaptic transmission, plasticity, and cognitive behavior, mostly likely due to a functional coupling with N-methyl-D-aspartate ( NMDA) receptors. In this study, we investigated the effects of reelin on the maturation of CA1 glutamatergic function using electrophysiological and biochemical approaches. In cultured hippocampal slices, reelin treatment increased the amplitude of AMPAR-mediated miniature excitatory postsynaptic currents and the evoked AMPA/NMDA receptor current ratios. In addition, reelin treatment also reduced the number of silent synapses, facilitated a developmental switch from NR2B to NR2A of NMDARs, and increased surface expression of AMPARs in CA1 tissue. In cultured hippocampal neurons from reeler embryos, reduced numbers of AMPAR subunit GluR1 and NMDAR subunit NR1 clustering were observed compared with those obtained from wild-type embryos. Supplementing reelin in the reeler culture obliterated these genotypic differences. These results demonstrate that reelin-and lipoprotein receptor-mediated signaling may operate during developmental maturation of hippocampal glutamatergic function and thus represent a potential important mechanism for controlling synaptic strength and plasticity in the postnatal hippocampus.