CPG15/Neuritin Mimics Experience in Selecting Excitatory Synapses for Stabilization by Facilitating PSD95 Recruitment.
CPG15/Neuritin Mimics Experience in Selecting Excitatory Synapses for Stabilization by Facilitating PSD95 Recruitment.
复制标题
CPG15/Neuritin 模仿通过促进 PSD95 招募来选择兴奋性突触以实现稳定的经验。
DOI：
10.1016/j.celrep.2019.07.012
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发表时间：
2019
期刊：
影响因子：
8.8
通讯作者：
Nedivi,Elly
中科院分区：
文献类型：
--
作者：
Subramanian,Jaichandar;Michel,Katrin;Benoit,Marc;Nedivi,Elly
大脑可塑性的一个关键特征是依赖于经验的最佳连接选择，这是由一组动态调节突触强度和数量的活动调节基因实现的。活性调节基因cpg15/neuritin先前被认为与兴奋性突触的稳定和成熟有关。在这里，我们将双光子显微镜与遗传和感觉操作结合起来，剖析体内兴奋性突触的形成，并检查活性和 CPG15 在树突棘形成、PSD95 招募和突触稳定中的作用。我们发现脊柱的形成既不需要视觉经验也不需要 CPG15。然而，PSD95 招募到新生棘及其随后的稳定需要两者。此外，细胞自主 CPG15 表达足以取代促进 PSD95 募集和脊柱稳定的经验。 CPG15 直接与未成熟树突棘上的 α-氨基-3-羟基-5-甲基-4-异恶唑丙酸 (AMPA) 受体相互作用，表明这种小细胞外分子的信号传导模式充当树突棘稳定和突触成熟的经验依赖性“选择器”。
A key feature of brain plasticity is the experience-dependent selection of optimal connections, implemented by a set of activity-regulated genes that dynamically adjust synapse strength and number. The activity-regulated genecpg15/neuritinhas been previously implicated in stabilization and maturation of excitatory synapses. Here, we combine two-photon microscopy with genetic and sensory manipulations to dissect excitatory synapse formationin vivoand examine the role of activity and CPG15 in dendritic spine formation, PSD95 recruitment, and synapse stabilization. We find that neither visual experience nor CPG15 is required for spine formation. However, PSD95 recruitment to nascent spines and their subsequent stabilization requires both. Further, cell-autonomous CPG15 expression is sufficient to replace experience in facilitating PSD95 recruitment and spine stabilization. CPG15 directly interacts with α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors on immature dendritic spines, suggesting a signaling mode for this small extracellular molecule acting as an experience-dependent "selector" for spine stabilization and synapse maturation.