International Center for Neurological Restoration, Havana, Cuba.
Neuroscience. 2010 Feb 17;165(4):1546-58. doi: 10.1016/j.neuroscience.2009.11.068. Epub 2009 Dec 3.
Hippocampal long-term potentiation (LTP) is a long-lasting increase in synaptic efficacy considered to be the cellular basis of memory. LTP consists of an early, protein synthesis-independent phase (E-LTP) and a late phase that depends on protein synthesis (L-LTP). In water-deprived rats E-LTP in the dentate gyrus (DG) can be reinforced into L-LTP, if the rats were allowed to drink within 15 min after E-LTP induction (behavioral LTP-reinforcement, BR). LTP can be depotentiated by low-frequency stimulation (LFS) to the same synaptic input if applied shortly after tetanization (<10 min). Here, we addressed the question of whether a BR protocol is able to recover LTP at depotentiated synaptic inputs. We show that LTP, depotentiation, LFS and BR specifically interact within one afferent input, which could be explained by the "synaptic tagging" hypothesis outlined by [Frey and Morris (1997) Nature 385:533-536]. E-LTP induced by a weak tetanus (WTET) sets tags in the activated inputs which are able to capture and to process plasticity-related proteins (PRPs) required for L-LTP, the synthesis of which was induced by BR. Synaptic tags could be reset by LFS. BR alone was unable to rescue depotentiated LTP, but the combination of BR and subsequent WTET transformed E-LTP into L-LTP. We show that LTP, LTD and behavioral stimuli alternatively and reversibly affect a single afferent input for long periods of time by LTP as well as LTD mechanisms, competing with each other under the influence of different concurrent stimuli. Affective modulation can shift the balance to one or the other. We show that the result will depend not only on the last stimulus, but on the history of previous stimuli applied to the specific input. Afferent stimuli activate alternative, but partially overlapping cascades with long-lasting consequences for the input including spaced-associative processes of "synaptic tagging" as well as "cross-tagging" which could be demonstrated in single synaptic afferents to one neuronal population in freely behaving animals.
海马长时程增强（LTP）是一种突触效能的持久增强，被认为是记忆的细胞基础。LTP 由一个早期、不依赖于蛋白质合成的阶段（E-LTP）和一个依赖于蛋白质合成的晚期阶段（L-LTP）组成。在缺水的大鼠中，如果在 E-LTP 诱导后 15 分钟内允许大鼠饮水（行为性 LTP 强化，BR），则齿状回（DG）中的 E-LTP 可以被强化为 L-LTP。如果在强直刺激后短时间内（<10 分钟）施加低频刺激（LFS）到相同的突触输入，LTP 可以被去极化。在这里，我们提出了一个问题，即 BR 方案是否能够恢复去极化突触输入的 LTP。我们表明，LTP、去极化、LFS 和 BR 可以在一个传入输入中特异性地相互作用，这可以用 [Frey 和 Morris（1997）自然 385:533-536] 提出的“突触标记”假说来解释。由弱强直刺激（WTET）诱导的 E-LTP 在激活的输入中设置标记，这些标记能够捕获和处理 L-LTP 所需的与可塑性相关的蛋白（PRPs），而 L-LTP 的合成是由 BR 诱导的。突触标记可以被 LFS 重置。BR 本身不能挽救去极化的 LTP，但 BR 与随后的 WTET 相结合，将 E-LTP 转化为 L-LTP。我们表明，LTP、LTD 和行为刺激通过 LTP 和 LTD 机制交替地、可逆地影响单个传入输入很长一段时间，在不同的并发刺激的影响下相互竞争。情感调节可以将平衡转移到一个或另一个方向。我们表明，结果不仅取决于最后一个刺激，还取决于施加到特定输入的先前刺激的历史。传入刺激激活了替代的、但部分重叠的级联，对输入产生持久的影响，包括“突触标记”和“交叉标记”的间隔联想过程，这些过程可以在自由行为动物的单个突触传入中得到证明。
