WM Keck Center for the Neurobiology of Learning and Memory, Department of Neurobiology and Anatomy, The University of Texas Medical School at Houston, Houston, Texas 77030, USA.
Learn Mem. 2010 Aug 24;17(9):428-39. doi: 10.1101/lm.1844010. Print 2010 Sep.
Memory consolidation and reconsolidation require kinase activation and protein synthesis. Blocking either process during or shortly after training or recall disrupts memory stabilization, which suggests the existence of a critical time window during which these processes are necessary. Using a computational model of kinase synthesis and activation, we investigated the ways in which the dynamics of molecular positive-feedback loops may contribute to the time window for memory stabilization and memory maintenance. In the models, training triggered a transition in the amount of kinase between two stable states, which represented consolidation. Simulating protein synthesis inhibition (PSI) from before to 40 min after training blocked or delayed consolidation. Beyond 40 min, substantial (>95%) PSI had little effect despite the fact that the elevated amount of kinase was maintained by increased protein synthesis. However, PSI made established memories labile to perturbations. Simulations of kinase inhibition produced similar results. In addition, similar properties were found in several other models that also included positive-feedback loops. Even though our models are based on simplifications of the actual mechanisms of molecular consolidation, they illustrate the practical difficulty of empirically measuring "time windows" for consolidation. This is particularly true when consolidation and reconsolidation of memory depends, in part, on the dynamics of molecular positive-feedback loops.
记忆的巩固和再巩固需要激酶的激活和蛋白质的合成。在训练或回忆过程中或之后不久阻断这两个过程会破坏记忆的稳定，这表明在这个过程中存在一个关键的时间窗口是必要的。我们使用激酶合成和激活的计算模型，研究了分子正反馈回路的动力学如何有助于记忆稳定和记忆维持的时间窗口。在模型中，训练触发了激酶在两种稳定状态之间的数量的转变，这代表了巩固。在训练前至 40 分钟模拟蛋白质合成抑制（PSI）会阻止或延迟巩固。超过 40 分钟后，尽管激酶的数量通过增加蛋白质合成来维持，但大量（>95%）的 PSI 几乎没有影响。然而，PSI 使已建立的记忆对干扰变得不稳定。激酶抑制的模拟产生了类似的结果。此外，在其他几个也包括正反馈回路的模型中也发现了类似的特性。尽管我们的模型是基于分子巩固的实际机制的简化，但它们说明了经验测量巩固的“时间窗口”的实际困难。当记忆的巩固和再巩固部分取决于分子正反馈回路的动力学时，情况尤其如此。
