CPG15 regulates synapse stability in the developing and adult brain
CPG15 regulates synapse stability in the developing and adult brain
复制标题
DOI：
10.1101/gad.176172.111
复制
发表时间：
2011-12-15
影响因子：
10.5
通讯作者：
Nedivi, Elly
中科院分区：
文献类型：
--
作者：
Fujino, Tadahiro;Leslie, Jennifer H.;Nedivi, Elly
最佳连接的依赖性选择是神经回路发育的一个关键特征，在成熟的大脑中，是功能适应的基础，例如学习和记忆所需的。活动模式通过选择性稳定或消除特定的神经元分支和突触来指导回路的完善。介导活动依赖性突触和乔木稳定和维持的分子信号仍然难以捉摸。我们报告，敲除小鼠的活性调节基因cpg15延迟轴突和树突状乔木的发育成熟，分别通过顺行追踪和diolistic标记。电生理学表明突触成熟也被延迟，电子显微镜证实许多树突棘最初缺乏功能性突触接触。虽然电路最终发展，在体内成像显示，脊柱的维护是在成年人妥协，导致脊柱数量逐渐磨损。cpg15的缺失也会导致学习不良。cpg15基因敲除小鼠需要更多的线索来学习，但一旦它们学会了，记忆就保留下来了。我们的研究结果表明，CPG15的行为，以稳定树突棘上的活性突触，导致选择性的棘和乔木稳定和突触成熟，和CPG15介导的突触稳定是有效的学习至关重要。
Use-dependent selection of optimal connections is a key feature of neural circuit development and, in the mature brain, underlies functional adaptation, such as is required for learning and memory. Activity patterns guide circuit refinement through selective stabilization or elimination of specific neuronal branches and synapses. The molecular signals that mediate activity-dependent synapse and arbor stabilization and maintenance remain elusive. We report that knockout of the activity-regulated gene cpg15 in mice delays developmental maturation of axonal and dendritic arbors visualized by anterograde tracing and diolistic labeling, respectively. Electrophysiology shows that synaptic maturation is also delayed, and electron microscopy confirms that many dendritic spines initially lack functional synaptic contacts. While circuits eventually develop, in vivo imaging reveals that spine maintenance is compromised in the adult, leading to a gradual attrition in spine numbers. Loss of cpg15 also results in poor learning. cpg15 knockout mice require more trails to learn, but once they learn, memories are retained. Our findings suggest that CPG15 acts to stabilize active synapses on dendritic spines, resulting in selective spine and arbor stabilization and synaptic maturation, and that synapse stabilization mediated by CPG15 is critical for efficient learning.