3月2日，《神经科学杂志》（The Journal of Neuroscience）发表了中科院上海生科院神经所神经元信息处理和可塑性研究组关于突触可塑性长时期维持的分子机制的最新发现。外界刺激引起的神经细胞持续的活动可以诱导突触传递的长时程改变，这一现象称之为长时程突触可塑性，并被认为是发育中神经环路精细修饰与学习记忆的细胞机制基础。根据突触长时程增强（LTP）持续的时间长短，通常可分为早期LTP和晚期LTP（late LTP, L-LTP）。其中，L-LTP持续超过数个小时直至数天，依赖于新蛋白合成，因此L-LTP是长时程记忆形成的细胞学基础。博士研究生龚利琴和何灵杰等通过在体检测视网膜-视顶盖兴奋性突触L-LTP的诱导和维持，发现（1）时间上以分钟间隔的持续突触活动更有利于L-LTP的诱导和维持；（2）突触“学习”后短时间（~30分钟）内突触后膜上N -甲基-D-天冬氨酸（NMDA）受体持续激活对于L-LTP稳定至关重要；同时 NMDA受体的激活依赖于“学习”后神经元的自发放电活动。先前人们认为NMDA受体激活只在突触可塑性的诱导期中发挥重要作用，这项研究的发现赋予了 NMDA受体在诱导期后的持续激活对维持突触可塑性长时程的关键作用。这些研究发现也为心理物理或行为学研究中所提出的“时间间隔”的学习形成长时程记忆的学说提供了突触“学习”机制。
该工作在神经所章晓辉研究组和蒲慕明研究组的共同合作下完成，并受到中科院“创新项目”（KSCX2-YW-R-29）和科技部“脑结构和功能的可塑性”973项目（2011CBA00400）的资助。（生物谷Bioon.com）
图注：突触可塑性的长期维持依赖诱导后短时间（30分钟）内NMDA受体的激活。
Rec：纪录电极；Sti：刺激电极；T：视顶盖；FB：前脑；3xTBS (5’)：3次五分钟间隔的θ束电刺激；D-AP-5：NMDA受体阻断剂，阴影表示加药时程。
生物谷推荐原文出处：
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.
