Dcf1 Triggers Dendritic Spine Formation and Facilitates Memory Acquisition
Dcf1 Triggers Dendritic Spine Formation and Facilitates Memory Acquisition
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DCf1 触发树突棘形成并促进记忆获取
DOI：
10.1007/s12035-016-0349-6
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发表时间：
2018-01-01
影响因子：
5.1
通讯作者：
Wen, Tieqiao
中科院分区：
文献类型：
--
作者：
Liu, Qiang;Feng, Ruili;Wen, Tieqiao
树突棘是神经细胞中的一种特殊结构，在执行细胞功能中起着关键作用。树突棘的结构异常可能导致突触功能障碍，并与记忆形成有关。然而，触发树突棘丢失的分子机制仍不清楚。在此，我们发现，树突状细胞因子1（Dcf 1）的缺失会导致树突棘发育异常，进而导致学习记忆功能的损害;相反，Dcf 1的表达增强可以挽救树突棘的形态和功能，表明Dcf 1在细胞功能中起着关键作用。电生理检测表明，Dcf 1（-/-）基因敲除（KO）小鼠的兴奋性突触后微电流频率明显降低。在光遗传学点燃之后，我们在Dcf 1 KO小鼠中观察到较弱的神经元激活，解释了神经回路原因。在分子机制上，我们发现Dcf 1通过募集Lcn 2和激活PSD 95-NMDAR信号通路来触发树突棘和突触功能。拆卸此制动器会导致内存损坏。我们的研究结果突出了树突棘发育和形成的一个意想不到的调节机制。
Dendritic spines, a special kind of structure in nerve cells, play a key role in performing cellular function. Structural abnormalities of the dendritic spine may contribute to synaptic dysfunction and have been implicated in memory formation. However, the molecular mechanisms that trigger dendritic spine loss remain unclear. Here, we show that the absence of dendritic cell factor 1 (Dcf1) appeared dendritic spines dysplasia, which in turn leads to the damage of learning and memory; in contrast, enhancing Dcf1 expression rescues dendritic spines morphology and function, indicating a pivotal role of Dcf1 in cellular function. Electrophysiological test indicates that there is a significant reduction in the frequency of miniature excitatory postsynaptic currents in Dcf1(-/-) knockout (KO) mice. Subsequent to optogenetic ignition, we observed a weaker neuronal activation in Dcf1 KO mice, explaining the neural circuit cause. On molecular mechanism, we demonstrated an unprecedented discovery that Dcf1 triggers the dendritic spine and synaptic function through the recruitment of Lcn2 and activation of PSD95-NMDAR signaling. Removing this brake leads to memory damage. Our results highlight an unexpected regulatory mechanism of dendritic spine development and formation.