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設計：李葉菲（南京大學本科實習生） 在最近一期的<neuron>雜志上，中國科學院上海生命科學院神經科學研究所的段樹民教授率領他的學生對沉默突觸的突觸前活化機制做了新的解釋。這也是中國科學家第一次在國際頂級期刊《神經元》上作為封面文章發表。文章的三個REVIEW一致作出了高度評價，并在本期雜志上專門為這篇文章做了綜述。 沈萬華，吳蓓等發現了一類與傳統認識上不同的沉默突觸。此種沉默突觸既不含NMDA受體，也不含AMPA受體，可以被神經元電活動依賴的突觸前刺激快速誘導活化，這一快速成熟的過程是由突觸前BDNF/Cdc42信號介導的actin聚合而完成。此類發現有助于解釋神經元發育過程中活化的機制，并為LTP的形成提供一個可以解釋的方向。為學習與記憶的形成和神經環路的調節提供神經基礎。 欣聞段樹民所在的突觸發育與可塑性組最近又有一篇文章被〈Science〉接受。在此表示熱烈的祝賀！ Volume 50 Issue 3: May 4 , 2006 Next Issue: May 18 Silent synapses are frequently found in the developing brain. Using paired patch-clamp recordings from cultured hippocampal neurons at an early development stage, Shen et al. identified nonfunctional contacts that lack both AMPA- and NMDA-mediated synaptic responses and are thus different from the conventional silent synapses containing NMDA-only responses. The authors show that presynaptic theta burst stimulation rapidly converts these contacts into functional synapses due to enhanced presynaptic glutamate release and actin polymerization induced by activation of BDNF-Cdc42 signaling at presynaptic release sites. These findings reveal a novel mechanism underlying activity-induced rapid presynaptic maturation during a critical stage of synapse formation. The context and implications of this study are discussed in a Preview by Atasoy and Kavalali. *Wanhua Shen, *Bei Wu, Zhijun Zhang, Ying Dou, Zhi-ren Rao, Yi-ren Chen Shumin Duan, Activity-induced rapid synaptic maturation mediated by presynaptic Cdc42 signaling. Neuron, 50,401-414. May 4, 2006. [Abstract][PDF] [PDF](*Co-author). (Note: This article was featured on this month's NEURON cover and Preview by Atasoy and Kavalali(May 4, 2006) Summary Maturation of presynaptic transmitter secretion machinery is a critical step in synaptogenesis. Here we report that a brief train of presynaptic action potentials rapidly converts early nonfunctional contacts between cultured hippocampal neurons into functional synapses by enhancing presynaptic glutamate release. The enhanced release was confirmed by a marked increase in the number of depolarization-induced FM4-64 puncta in the presynaptic axon. This rapid presynaptic maturation can be abolished by treatments that interfered with presynaptic BDNF and Cdc42 signaling or actin polymerization. Activation of Cdc42 by applying BDNF or bradykinin mimicked the effect of electrical activity in promoting synaptic maturation. Furthermore, activity-induced increase in presynaptic actin polymerization, as revealed by increased concentration of actin-YFP at axon boutons, was abolished by inhibiting BDNF and Cdc42 signaling. Thus, rapid presynaptic maturation induced by neuronal activity is mediated by presynaptic activation of the Cdc42 signaling pathway. 中文摘要： 突觸前遞質釋放裝置的發育成熟和突觸后受體的轉運是中樞神經系統突觸發育過程中非常重要的兩個方面。普遍認為，在神經元的發育早期，大多數突觸后膜上只含NMDA受體而不含AMPA受體。隨著神經系統的發育成熟，AMPA受體的轉運上膜后才有大量功能性突觸的產生。研究者也習慣的把只含NMDA受體的突觸定義為沉默突觸（silent synapse）。大量研究表明，AMPA受體的上膜所導致的沉默突觸活化機制也是LTP形成的神經基礎，沉默突觸的形成和活化機制研究在神經可塑性領域已經受到了很大的重視，闡述清楚沉默突觸的活化過程也為研究LTP相關的學習記憶提供了基本條件。雖然突觸前在沉默突觸活化過程中的作用也已經得到重視，但其具體的活化機制和介導的信號通路還不清楚。 我們運用雙膜片鉗技術同時記錄兩個培養的海馬神經元，發現了和傳統認識上不同的一類沉默突觸，即該類突觸既沒有NMDA受體介導的反應，也沒有AMPA受體介導的反應。當在突觸前注入TBS后，能快速的誘導此類沉默突觸轉化為功能性突觸，并進一步揭示了這種轉變需要突觸前BDNF/Cdc42信號的參與。為進一步探索這種轉變的分子機制，我們用FM4-64標記實驗證明了突觸前有新的功能性囊泡增加，此過程和Cdc42介導的突觸前肌動蛋白微絲（actin）的聚合有關。actin-YFP熒光變化的動態觀察實驗證實了這種突觸前活性依賴的肌動蛋白聚合可以被BDNF及Cdc42信號通路的阻斷劑阻斷。FM4-64標記的功能性囊泡與突觸前囊泡蛋白SNP的共定位實驗結果表明，電場刺激（EFS）或BDNF誘導的功能性囊泡增加是因為促進了準備釋放囊泡庫（RRP）處的囊泡成熟。電鏡實驗進一步直接觀察到了電活動依賴的活性帶區的可釋放囊泡的增加。 綜上所述，本文發現了一類與傳統認識上不同的沉默突觸。此種沉默突觸既不含NMDA受體，也不含AMPA受體，可以被神經元電活動依賴的突觸前刺激快速誘導活化，這一快速成熟的過程是由突觸前BDNF/Cdc42信號介導的actin聚合而完成。因此，本文揭示了神經發育過程中沉默突觸活化的新機制，對進一步研究突觸發育以及神經回路的形成具有一定的指導意義。 Xu, X., Fu, A., Ip, F., Wu, C., Duan, S., Poo, M., Yuan, X., and Ip, N. (2005) Agrin regulates growth cone turning of Xenopus spinal motoneurons. Development 132: 4309-4316. Pan, P., Cai, Q., Lin, L., Lu, P., Duan, S., and Sheng, Z. (2005) SNAP-29-mediated Modulation of Synaptic Transmission in Cultured Hippocampal Neurons. J. Biol.Chem. 280: 25769-25779. Li, C., Lu, J., Wu, J., Duan, S., and Poo, M. (2004) Bidirectional Modification of Presynaptic Neuronal Excitability Accompanying Spike Timing-Dependent Synaptic Plasticity. Neuron 41, 257-268. Yang, Y., Ge, W., Chen, Y., Zhang, Z., Shen, W., Wu, C., Poo, M., and Duan, S. (2003) Contribution of astrocytes to hippocampal long-term potentiation through release of D-serine. PNAS, 100: 15194-15199. Zhang, J., Wang, H., Ye, C., Ge, W., Chen, Y., Jiang, Z., Wu, C., Poo, M. and Duan, S. (2003) ATP Released by Astrocytes Mediates Glutamatergic Activity-Dependent Heterosynaptic Suppression. Neuron, 40: 971-982. Duan, S., Anderson C. M. , Keung, E. C., Chen, Y., Chen, Y., and Swanson R. A.(2003) P2X7 Receptor-Mediated Release of Excitatory Amino Acids from Astrocytes. J Neurosci, 23: 1320-1328 Wang, Z., Xu, N., Wu,CP., Duan, S., and Poo, M. (2003) Bidirectional changes in spatial dendritic integration accompanying long-term synaptic modifications. Neuron, 37: 463-472 Yuan, X., Jin, M., Xu, X., Wu, CP., Poo, M., and Duan, S.(2003) Signalling and crosstalk of Rho GTPases in mediating axon guidance. Nature Cell Biol , 5, 38 - 45 [Abstract] |
