中科院神經(jīng)所于翔課題組近期的工作表明,，Wnt信號(hào)的傳導(dǎo)分子β-catenin 蛋白,，及由 cadherin，β-catenin 和 α-catenin 組成的細(xì)胞粘附復(fù)合物,，是調(diào)節(jié)樹(shù)突形態(tài)的重要介導(dǎo)物。在分離的海馬神經(jīng)元中增加細(xì)胞內(nèi) cadherin/catenin 復(fù)合物的含量可以增強(qiáng)樹(shù)突的樹(shù)狀分支程度,；相反,，過(guò)表達(dá) Ncad(intra)，一種可隔離阻斷 β-catenin 功能的分子,，則導(dǎo)致樹(shù)突分支末端數(shù)目的減少，并且阻止模擬神經(jīng)活動(dòng)或激活 Wnt 信號(hào)傳遞所引起的樹(shù)突形態(tài)發(fā)生的增強(qiáng),。實(shí)驗(yàn)結(jié)果還顯示，模擬神經(jīng)活動(dòng)的增強(qiáng)(增加細(xì)胞外液鉀離子的濃度,，從而使神經(jīng)元去極化)可以提高細(xì)胞培養(yǎng)液中的 Wnt 活性,，顯示神經(jīng)活動(dòng)可能調(diào)節(jié) Wnt 的基因表達(dá),。
而這篇文章則主要針對(duì)形態(tài)學(xué)與功能學(xué)的相互關(guān)系,，神經(jīng)環(huán)路發(fā)育需要形態(tài)學(xué)方面和功能上的改變,，研究人員發(fā)現(xiàn)了提高神經(jīng)活性之后,，樹(shù)突形態(tài)學(xué)和mEPSC (miniature excitatory post-synaptic current,，微小興奮性突觸后電流)變化之間的相對(duì)應(yīng)關(guān)系,。并且發(fā)現(xiàn)β-catenin分子的過(guò)量表達(dá),，與通過(guò)降低mEPSC變化幅度一樣，都能達(dá)到增加神經(jīng)活性的作用,。
更加重要的是，研究人員還發(fā)現(xiàn)β-catenin體內(nèi)過(guò)表達(dá)能促進(jìn)樹(shù)突生長(zhǎng),，減少mEPSC變化幅度,，從而研究人員提出，這些數(shù)據(jù)證明樹(shù)突形態(tài)學(xué)和單一刺激突觸強(qiáng)度的同樣變化也許都是避免神經(jīng)元在神經(jīng)環(huán)路發(fā)育過(guò)程中過(guò)于興奮的一種重要機(jī)制,。
這項(xiàng)研究通過(guò)體內(nèi)和體外研究，結(jié)合分子生物學(xué),、光學(xué)成像,、電生理學(xué)等手段闡述樹(shù)突形態(tài)發(fā)生的分子機(jī)制及其對(duì)突觸功能和神經(jīng)環(huán)路形成的影響,，將更清晰地闡明樹(shù)突發(fā)育和神經(jīng)環(huán)路形成的分子機(jī)制，并將有助于對(duì)發(fā)育性神經(jīng)疾病的理解,。（生物谷Bioon.com）
生物谷推薦原始出處：
Neuron, Volume 61,15 January 2009 doi:10.1016/j.neuron.2008.11.015
Coordinated Changes in Dendritic Arborization and Synaptic Strength during Neural Circuit Development
Yi-Rong Peng1,2,Shan He1,2,Helene Marie3,4,Si-Yu Zeng1,2,Jun Ma1,Zhu-Jun Tan1,2,Soo Yeun Lee3,Robert C. Malenka3,,andXiang Yu1,5,,
1 Institute of Neuroscience and State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China
2 Graduate School of the Chinese Academy of Sciences, Shanghai 200031, China
3 Nancy Pritzker Laboratory, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Palo Alto, CA 94304-5485, USA
4 Present address: European Brain Research Institute, Rome 00143, Italy
5 Previous address: Nancy Pritzker Laboratory, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Palo Alto, CA 94304-5485, USA
Neural circuit development requires concurrent morphological and functional changes. Here, we identify coordinated and inversely correlated changes in dendritic morphology and mEPSC amplitude following increased neural activity. We show that overexpression of -catenin, a molecule that increases total dendritic length, mimics the effects of increased neuronal activity by scaling down mEPSC amplitudes, while postsynaptic expression of a protein that sequesters -catenin reverses the effects of activity on reducing mEPSC amplitudes. These results were confirmed immunocytochemically as changes in the size and density of surface synaptic AMPA receptor clusters. In individual neurons there was an inverse linear relationship between total dendritic length and average mEPSC amplitude. Importantly, -catenin overexpression invivo promoted dendritic growth and reduced mEPSC amplitudes. Together, these results demonstrate that coordinated changes in dendritic morphology and unitary excitatory synaptic strength may serve as an important intrinsic mechanism that helps prevent neurons from overexcitation during neural circuit development.
