Laboratory of molecular neural biology, School of life sciences, Shanghai University, 333 Nanchen Road, Shanghai, 200444, China.
Department of Anatomy and Neurobiology, Tongji University School of Medicine, 1239 SiPing Road, Shanghai, 200092, China.
Mol Neurobiol. 2018 Jan;55(1):763-775. doi: 10.1007/s12035-016-0349-6. Epub 2017 Jan 5.
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.
树突棘是神经细胞中的一种特殊结构，在执行细胞功能方面发挥着关键作用。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，触发树突棘缺失的分子机制尚不清楚。在这里，我们发现树突细胞因子 1（Dcf1）的缺失会导致树突棘发育不良，进而导致学习和记忆受损；相反，增强 Dcf1 的表达可以挽救树突棘的形态和功能，表明 Dcf1 在细胞功能中起着关键作用。电生理测试表明，Dcf1 敲除（KO）小鼠的微小兴奋性突触后电流频率显著降低。随后进行光遗传学点火，我们观察到 Dcf1 KO 小鼠中的神经元激活较弱，解释了神经回路的原因。在分子机制上，我们证明了一个前所未有的发现，即 Dcf1 通过募集 Lcn2 和激活 PSD95-NMDAR 信号来触发树突棘和突触功能。消除这种阻碍会导致记忆损伤。我们的研究结果突出了树突棘发育和形成的一种意外调节机制。
