Postinduction requirement of NMDA receptor activation for late-phase long-term potentiation of developing retinotectal synapses in vivo.
Postinduction requirement of NMDA receptor activation for late-phase long-term potentiation of developing retinotectal synapses in vivo.
复制标题
DOI：
10.1523/jneurosci.5936-10.2011
复制
发表时间：
2011-03-02
期刊：
影响因子：
--
通讯作者：
Zhang XH
中科院分区：
文献类型：
--
作者：
Gong LQ;He LJ;Dong ZY;Lu XH;Poo MM;Zhang XH
重复性突触激活的间隔模式通常会导致持久的、依赖于蛋白质合成的突触传递增强，称为后期长期增强（L-LTP），可以作为长期记忆的基础。行为研究表明，训练后阻断谷氨酸受体 (NMDAR) 的 NMDAR 亚型会损害长期记忆，尽管众所周知在 LTP 诱导过程中需要激活 NMDAR。在这项研究中，我们发现体内L-LTP的建立需要在LTP诱导后的关键时间窗口内激活NMDAR。在非洲爪蟾蝌蚪正在发育的视觉系统中，视网膜顶盖突触的L-LTP可以通过视神经间隔5分钟的θ爆发刺激（TBS）（“间隔TBS”）诱导3次，但不能通过集体应用或间隔≥10分钟的3次TBS诱导。在“间隔 TBS”后约 30 分钟的时间窗口内，顶盖局部灌注 NMDAR 拮抗剂 d-AP5 或 Ca2+-螯合剂 EGTA-AM 损害了 L-LTP 的建立，表明需要诱导后激活 NMDAR/Ca2+ 信号传导。此外，当“间隔TBS”后立即应用TTX 15分钟而不是1小时后，通过局部应用河豚毒素（TTX）抑制顶盖中的自发尖峰活动可预防L-LTP，而在视网膜中相同的诱导后应用TTX则没有效果。这些发现为 NMDAR 学习后激活需求的突触基础提供了新的见解，并指出了学习后自发回路活动在记忆形成中的重要性。
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 post-training blockade of n-methyl d-aspartate 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 following 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 post-induction 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 following the “spaced TBS” but not 1 hr later, whereas the same post-induction TTX application in the retina had no effect. These findings offer new insights into the synaptic basis for the requirement of post-learning activation of NMDARs, and point to the importance of post-learning spontaneous circuit activity in memory formation.