Neuronal pentraxins mediate synaptic refinement in the developing visual system
Neuronal pentraxins mediate synaptic refinement in the developing visual system
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DOI：
10.1523/jneurosci.4212-05.2006
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发表时间：
2006-06-07
影响因子：
5.3
通讯作者：
Perin, Mark S.
中科院分区：
文献类型：
--
作者：
Bjartmar, Lisa;Huberman, Andrew D.;Perin, Mark S.
神经元五聚蛋白（NPs）定义了一个蛋白质家族，与免疫系统中的C反应蛋白和急性期蛋白同源，并被假设参与活性依赖性突触可塑性。为了研究NP在体内的作用，我们产生了缺乏一种、两种或所有三种NP的小鼠。NP 1/2基因敲除小鼠表现出眼特异性视网膜神经节细胞（RGC）投射到背外侧膝状体核的分离缺陷，这是一个涉及活动依赖性突触形成和消除的过程。缺乏NP 1和NP 2的小鼠的视网膜具有胆碱能驱动的活动波，其发生频率与野生型小鼠相似，但视网膜活动的其他几个参数发生了改变。从这些小鼠培养的RGCs表现出显着延迟的突触功能成熟。其他发育过程，如视交叉和海马长时程增强和长时程抑制的RGCs的寻路，在NP缺陷小鼠中似乎正常。这些数据表明，NP是必要的哺乳动物视网膜和背外侧膝状体核的早期突触细化。我们推测，纳米粒子发挥其作用的机制，平行的短pentraxins外的中枢神经系统的作用。
Neuronal pentraxins (NPs) define a family of proteins that are homologous to C-reactive and acute-phase proteins in the immune system and have been hypothesized to be involved in activity-dependent synaptic plasticity. To investigate the role of NPs in vivo, we generated mice that lack one, two, or all three NPs. NP1/2 knock-out mice exhibited defects in the segregation of eye-specific retinal ganglion cell (RGC) projections to the dorsal lateral geniculate nucleus, a process that involves activity-dependent synapse formation and elimination. Retinas from mice lacking NP1 and NP2 had cholinergically driven waves of activity that occurred at a frequency similar to that of wild-type mice, but several other parameters of retinal activity were altered. RGCs cultured from these mice exhibited a significant delay in functional maturation of glutamatergic synapses. Other developmental processes, such as pathfinding of RGCs at the optic chiasm and hippocampal long-term potentiation and long-term depression, appeared normal in NP-deficient mice. These data indicate that NPs are necessary for early synaptic refinements in the mammalian retina and dorsal lateral geniculate nucleus. We speculate that NPs exert their effects through mechanisms that parallel the known role of short pentraxins outside the CNS.