3月2日，《神經(jīng)科學(xué)雜志》（The Journal of Neuroscience）發(fā)表了中科院上海生科院神經(jīng)所神經(jīng)元信息處理和可塑性研究組關(guān)于突觸可塑性長時期維持的分子機制的最新發(fā)現(xiàn),。外界刺激引起的神經(jīng)細胞持續(xù)的活動可以誘導(dǎo)突觸傳遞的長時程改變,，這一現(xiàn)象稱之為長時程突觸可塑性，并被認為是發(fā)育中神經(jīng)環(huán)路精細修飾與學(xué)習(xí)記憶的細胞機制基礎(chǔ),。根據(jù)突觸長時程增強（LTP）持續(xù)的時間長短,，通常可分為早期LTP和晚期LTP（late LTP, L-LTP）,。其中,，L-LTP持續(xù)超過數(shù)個小時直至數(shù)天，依賴于新蛋白合成,，因此L-LTP是長時程記憶形成的細胞學(xué)基礎(chǔ),。博士研究生龔利琴和何靈杰等通過在體檢測視網(wǎng)膜-視頂蓋興奮性突觸L-LTP的誘導(dǎo)和維持，發(fā)現(xiàn)（1）時間上以分鐘間隔的持續(xù)突觸活動更有利于L-LTP的誘導(dǎo)和維持,；（2）突觸“學(xué)習(xí)”后短時間（~30分鐘）內(nèi)突觸后膜上N -甲基-D-天冬氨酸（NMDA）受體持續(xù)激活對于L-LTP穩(wěn)定至關(guān)重要,；同時 NMDA受體的激活依賴于“學(xué)習(xí)”后神經(jīng)元的自發(fā)放電活動。先前人們認為NMDA受體激活只在突觸可塑性的誘導(dǎo)期中發(fā)揮重要作用,，這項研究的發(fā)現(xiàn)賦予了 NMDA受體在誘導(dǎo)期后的持續(xù)激活對維持突觸可塑性長時程的關(guān)鍵作用,。這些研究發(fā)現(xiàn)也為心理物理或行為學(xué)研究中所提出的“時間間隔”的學(xué)習(xí)形成長時程記憶的學(xué)說提供了突觸“學(xué)習(xí)”機制。
該工作在神經(jīng)所章曉輝研究組和蒲慕明研究組的共同合作下完成,，并受到中科院“創(chuàng)新項目”（KSCX2-YW-R-29）和科技部“腦結(jié)構(gòu)和功能的可塑性”973項目（2011CBA00400）的資助,。（生物谷Bioon.com）
圖注：突觸可塑性的長期維持依賴誘導(dǎo)后短時間（30分鐘）內(nèi)NMDA受體的激活。
Rec：紀錄電極,；Sti：刺激電極,；T：視頂蓋,；FB：前腦；3xTBS (5’)：3次五分鐘間隔的θ束電刺激,；D-AP-5：NMDA受體阻斷劑,，陰影表示加藥時程。
生物谷推薦原文出處：
J Neurosci. 2011 Mar 2;31(9):3328-35.
Postinduction Requirement of NMDA Receptor Activation for Late-Phase Long-Term Potentiation of Developing Retinotectal Synapses In Vivo
Gong LQ, He LJ, Dong ZY, Lu XH, Poo MM, Zhang XH.
Spaced patterns of repetitive synaptic activation often result in a long-lasting, protein synthesis-dependent potentiation of synaptic transmission, known as late-phase long-term potentiation (L-LTP) that may serve as a substrate for long-term memory. Behavioral studies showed that posttraining blockade of NMDA subtype of the glutamate receptor (NMDAR) impaired long-term memory, although NMDAR activation is generally known to be required during LTP induction. In this study, we found that the establishment of L-LTP in vivo requires NMDAR activation within a critical time window after LTP induction. In the developing visual system of Xenopus laevis tadpole, L-LTP of retinotectal synapses could be induced by three episodes of theta burst stimulation (TBS) of the optic nerve with 5 min spacing ("spaced TBS"), but not by three TBS episodes applied en masse or spaced with intervals ≥10 min. Within a time window of ~30 min after the spaced TBS, local perfusion of the tectum with NMDAR antagonist d-AP5 or Ca2+-chelator EGTA-AM impaired the establishment of L-LTP, indicating the requirement of postinduction activation of NMDAR/Ca2+ signaling. Moreover, inhibiting spontaneous spiking activity in the tectum by local application of tetrodotoxin (TTX) prevented L-LTP when TTX was applied for 15 min immediately after the spaced TBS but not 1 h later, whereas the same postinduction TTX application in the retina had no effect. These findings offer new insights into the synaptic basis for the requirement of postlearning activation of NMDARs and point to the importance of postlearning spontaneous circuit activity in memory formation.
