神經(jīng)元突觸結(jié)構(gòu)產(chǎn)生的持續(xù)變化被認為是我們大腦學習和記憶的基礎(chǔ),。在這個問題上,Ataman等人研究了谷氨酸對果蠅的神經(jīng)肌肉突觸結(jié)構(gòu)與功能的影響,,發(fā)現(xiàn)由活動依賴性Wnt釋放引發(fā)的突觸結(jié)構(gòu)與功能,級聯(lián)啟動了突觸前后細胞不同的Wnt信號,。
在神經(jīng)元的突觸結(jié)構(gòu)中,,活動依賴性的調(diào)節(jié)作用在突觸發(fā)育和可塑性方面發(fā)揮著關(guān)鍵作用。然而,,這種調(diào)節(jié)作用所涉及的信號傳導的機制人們卻了解甚少,。Ataman等人的最新研究表明,谷氨酸能使果蠅神經(jīng)肌肉的接合點在響應定位刺激時,,產(chǎn)生突觸結(jié)構(gòu)和功能的快速變化,。這種依賴轉(zhuǎn)錄和翻譯的變化包括動力型突觸前絲狀偽足的形成和未分化神經(jīng)膨體的修飾,以及自發(fā)釋放頻率的增強等,。
研究表明,,一個雙向Wnt/Wg信號通路是這些變化的基礎(chǔ)。引起這些變化的同時會促使Wnt/Wg從突觸終扣中釋放,,這就刺激了一個突觸后的DFz2核進入通路,,以及一個涉及GSK-3β/Shaggy的突觸后通路,。Ataman等的研究結(jié)果顯示,雙向的Wg信號傳導在后期對神經(jīng)活動引起的突觸結(jié)構(gòu)與功能變化起調(diào)節(jié)作用,。他們還指出,,突觸后Wg通路的活動需要突觸后元件的組裝,同時突觸后Wg通路的活動也可以作用于細胞骨架動力學,。
相關(guān)論文以封面文章形式發(fā)表在3月13日的《神經(jīng)元》(Neuron)雜志上,。(科學網(wǎng) 武彥文/編譯)
生物谷推薦原始出處:
(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.