神经元突触结构产生的持续变化被认为是我们大脑学习和记忆的基础。在这个问题上,Ataman等人研究了谷氨酸对果蝇的神经肌肉突触结构与功能的影响,发现由活动依赖性Wnt释放引发的突触结构与功能,级联启动了突触前后细胞不同的Wnt信号。
在神经元的突触结构中,活动依赖性的调节作用在突触发育和可塑性方面发挥着关键作用。然而,这种调节作用所涉及的信号传导的机制人们却了解甚少。Ataman等人的最新研究表明,谷氨酸能使果蝇神经肌肉的接合点在响应定位刺激时,产生突触结构和功能的快速变化。这种依赖转录和翻译的变化包括动力型突触前丝状伪足的形成和未分化神经膨体的修饰,以及自发释放频率的增强等。
研究表明,一个双向Wnt/Wg信号通路是这些变化的基础。引起这些变化的同时会促使Wnt/Wg从突触终扣中释放,这就刺激了一个突触后的DFz2核进入通路,以及一个涉及GSK-3β/Shaggy的突触后通路。Ataman等的研究结果显示,双向的Wg信号传导在后期对神经活动引起的突触结构与功能变化起调节作用。他们还指出,突触后Wg通路的活动需要突触后元件的组装,同时突触后Wg通路的活动也可以作用于细胞骨架动力学。
相关论文以封面文章形式发表在3月13日的《神经元》(Neuron)杂志上。(科学网 武彦文/编译)
生物谷推荐原始出处:
(Neuron),Vol 57, 705-718, 13 March 2008,Bulent Ataman, Vivian Budnik
Rapid Activity-Dependent Modifications in Synaptic Structure and Function Require Bidirectional Wnt Signaling
Bulent Ataman,1 James Ashley,1,3 Michael Gorczyca,1,3 Preethi Ramachandran,1 Wernher Fouquet,2 Stephan J. Sigrist,2 and Vivian Budnik1,
1 Department of Neurobiology, University of Massachusetts Medical School, Worcester, MA 01605, USA
2 Institut für Klinische Neurobiologie und Rudolf-Virchow-Zentrum, Universität Würzburg, D-97078 Würzburg, Germany
Summary
Activity-dependent modifications in synapse structure play a key role in synaptic development and plasticity, but the signaling mechanisms involved are poorly understood. We demonstrate that glutamatergic Drosophila neuromuscular junctions undergo rapid changes in synaptic structure and function in response to patterned stimulation. These changes, which depend on transcription and translation, include formation of motile presynaptic filopodia, elaboration of undifferentiated varicosities, and potentiation of spontaneous release frequency. Experiments indicate that a bidirectional Wnt/Wg signaling pathway underlies these changes. Evoked activity induces Wnt1/Wg release from synaptic boutons, which stimulates both a postsynaptic DFz2 nuclear import pathway as well as a presynaptic pathway involving GSK-3β/Shaggy. Our findings suggest that bidirectional Wg signaling operates downstream of synaptic activity to induce modifications in synaptic structure and function. We propose that activation of the postsynaptic Wg pathway is required for the assembly of the postsynaptic apparatus, while activation of the presynaptic Wg pathway regulates cytoskeletal dynamics.