科學(xué)家找到了將經(jīng)歷與認(rèn)知聯(lián)系起來(lái)的分子機(jī)制,。
（圖片提供：CORBIS）
大腦如何形成一次記憶,？通常，我們的經(jīng)歷和相互作用會(huì)以某種方式在大腦中留下烙印,，然而神經(jīng)細(xì)胞究竟是如何改變它們的連接從而形成記憶,，卻一直是個(gè)未解之謎。如今,，科學(xué)家表示,，他們找到了將經(jīng)歷與認(rèn)知聯(lián)系起來(lái)的分子機(jī)制，而這一切似乎全部要?dú)w功于一臺(tái)微小的分子發(fā)動(dòng)機(jī),。
科學(xué)家相信,，記憶的存儲(chǔ)與一個(gè)名為長(zhǎng)時(shí)程增強(qiáng)（LTP）的過(guò)程有關(guān)，該過(guò)程強(qiáng)化了神經(jīng)細(xì)胞對(duì)之間的聯(lián)系,。神經(jīng)細(xì)胞通過(guò)釋放神經(jīng)傳遞素——用于刺激周?chē)?ldquo;鄰居”的受體——來(lái)進(jìn)行交流,，而LTP能夠觸發(fā)更多的受體聚集在接收細(xì)胞的細(xì)胞膜上，從而使其對(duì)于到來(lái)的信息更為敏感,。
之前的研究表明,，肌動(dòng)蛋白和肌球蛋白——在肌肉收縮中扮演重要角色的兩種蛋白質(zhì)——在神經(jīng)細(xì)胞的受體積聚過(guò)程中起到了關(guān)鍵作用。為了研究這種可能性,，美國(guó)北卡羅萊納州達(dá)勒姆市杜克大學(xué)醫(yī)學(xué)中心的神經(jīng)生物學(xué)家Michael Ehlers和他的同事，利用定時(shí)成像和生物化學(xué)方法,，對(duì)小鼠的大腦切片進(jìn)行了研究,。這些試驗(yàn)顯示，一個(gè)引入的信號(hào)能夠觸發(fā)大量的鈣進(jìn)入一個(gè)神經(jīng)細(xì)胞,。這些鈣會(huì)激活一種肌球蛋白——肌球蛋白Vb,，從而促使它獲得儲(chǔ)存在細(xì)胞深處的受體包，并將這些受體包帶到神經(jīng)細(xì)胞的信號(hào)位點(diǎn),，在這里,，受體能夠接收神經(jīng)傳遞素，并參與LTP過(guò)程。
為證實(shí)肌球蛋白Vb的確是讓認(rèn)知過(guò)程變?yōu)榭赡艿陌l(fā)動(dòng)機(jī),，Ehlers和他的同事利用化學(xué)方法抑制神經(jīng)細(xì)胞中的肌球蛋白Vb,，這些細(xì)胞于是便無(wú)法產(chǎn)生LTP。研究人員在最新一期的《細(xì)胞》雜志上報(bào)告了這一研究成果,。Ehlers指出：“對(duì)于一個(gè)馬達(dá)分子竟然能夠解釋大多數(shù)的膜傳輸過(guò)程,，我們感到非常驚訝。事實(shí)上,，它很可能就是形成記憶的‘發(fā)動(dòng)機(jī)’,。”
在美國(guó)亞拉巴馬州奧本大學(xué)從事細(xì)胞信號(hào)研究的神經(jīng)生物學(xué)家Marie Wooten認(rèn)為：“研究人員所做的工作將許多點(diǎn)連接在一起。”Wooten指出,，這篇論文一層一層地展示了,，神經(jīng)細(xì)胞如何在LTP期間將受體轉(zhuǎn)移到它們的外部膜。夏洛茨維爾市弗吉尼亞大學(xué)的神經(jīng)科學(xué)家Bettina Winckler對(duì)此表示贊同,。Winckler表示,，“這篇論文就像是一塊鉆石”，或者說(shuō)是一臺(tái)設(shè)計(jì)完美的發(fā)動(dòng)機(jī),。她說(shuō)：“它能夠完美地適應(yīng)每件事物,。”（生物谷Bioon.com）
生物谷推薦原始出處：
Cell, Volume 135, Issue 3, 535-548, 31 October 2008 doi:10.1016/j.cell.2008.09.057
Myosin Vb Mobilizes Recycling Endosomes and AMPA Receptors for Postsynaptic Plasticity
Zhiping Wang1,2,Jeffrey G. Edwards3,6,Nathan Riley3,D. William Provance4,Ryan Karcher4,Xiang-dong Li5,Ian G. Davison1,2,Mitsuo Ikebe5,John A. Mercer4,Julie A. Kauer3andMichael D. Ehlers1,2,,
1 Department of Neurobiology, Duke University Medical Center, Durham, NC 27710, USA
2 Howard Hughes Medical Institute, Duke University Medical Center, Durham, NC 27710, USA
3 Department of Molecular Pharmacology, Physiology, and Biotechnology, Brown University, Providence, RI 02912, USA
4 McLaughlin Research Institute, Great Falls, MT 59405, USA
5 Department of Physiology, University of Massachusetts Medical School, Worcester, MA 01655, USA
Corresponding author
6 Present address: Department of Physiology and Developmental Biology, Brigham Young University, 575 WIDB, Provo, UT 84602, USA
SUMMARY
Learning-related plasticity at excitatory synapses in the mammalian brain requires the trafficking of AMPA receptors and the growth of dendritic spines. However, the mechanisms that couple plasticity stimuli to the trafficking of postsynaptic cargo are poorly understood. Here we demonstrate that myosin Vb (MyoVb), a Ca2+-sensitive motor, conducts spine trafficking during long-term potentiation (LTP) of synaptic strength. Upon activation of NMDA receptors and corresponding Ca2+ influx, MyoVb associates with recycling endosomes (REs), triggering rapid spine recruitment of endosomes and local exocytosis in spines. Disruption of MyoVb or its interaction with the RE adaptor Rab11-FIP2 abolishes LTP-induced exocytosis from REs and prevents both AMPA receptor insertion and spine growth. Furthermore, induction of tight binding of MyoVb to actin using an acute chemical genetic strategy eradicates LTP in hippocampal slices. Thus, Ca2+-activated MyoVb captures and mobilizes REs for AMPA receptor insertion and spine growth, providing a mechanistic link between the induction and expression of postsynaptic plasticity.
