Long-lasting memory from evanescent networks.
Long-lasting memory from evanescent networks.
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来自转瞬即逝的网络的持久记忆。
DOI：
10.1016/j.ejphar.2008.02.047
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发表时间：
2008
影响因子：
5
通讯作者：
Routtenberg,Aryeh
中科院分区：
文献类型：
--
作者：
Routtenberg,Aryeh
目前的记忆模型通常需要一个蛋白质合成步骤，导致代表存储信息的神经网络突触发生或多或少永久的结构变化。这种蛋白质合成的指导作用最近受到质疑[Routtenberg， A., Rekart， J.L. 2005]。突触蛋白翻译后修饰作为持久记忆的底物。神经科学进展，28,12-19]。取而代之的是一种新的理论，其中已经合成并存在于突触内的蛋白质的翻译后修饰（PTMs）校准突触强度。因此，PTM是维持持久记忆所需的唯一机制。脑突触内活动诱导的、依赖于ptm的结构修饰定义了网络的形成，因此这是级联ptm串联的产物。这导致了一种不同于当前蛋白质合成模型的公式，其中神经网络最初是由这些个体突触ptm依赖的变化形成的，由调节的正反馈维持。一种这样的积极反馈机制是“隐式排练”，通常被称为“噪音”或“自发”活动。这种活动实际上不是随机的或自发的，而是由神经细胞过去的激活历史在随机意义上决定的。为了防止混杂网络的形成，调节的正反馈维持了给定特定衰变动力学的PTM的改变状态。单个突触的上行或下行状态实际上存在于无数种中间状态中，既不是完全“上行”，也不是完全“下行”。因此，由这些不确定的突触形成的网络是亚稳态的。一个特定的内存也用“简并码”相乘表示，这样如果出现表征子集的丢失，就可以防止擦除。这种机制也解决了灵活性-稳定性的问题，假设大脑避免了突触的稳定性，它有自己的不确定性原理，允许从概率网络中检索，因此检索到的记忆可以由从本质上无限数量的网络中选择的组件来表示。这样形成的网络，即检索，就从连接概率的层次中产生。这种记忆网络形成的新理论与当前和潜在的计算实现的关系将受益于其不同寻常的起始点：对信息存储的分子底物的深刻关注。
Current models of memory typically require a protein synthetic step leading to a more or less permanent structural change in synapses of the network that represent the stored information. This instructive role of protein synthesis has recently been called into question [Routtenberg, A., Rekart, J.L. 2005. Post-translational modification of synaptic proteins as the substrate for long-lasting memory. Trends Neurosci. 28, 12–19]. In its place a new theory is proposed in which post-translational modifications (PTMs) of proteins already synthesized and present within the synapse calibrate synaptic strength. PTM is thus the only mechanism required to sustain long-lasting memories. Activity-induced, PTM-dependent structural modifications within brain synapses then define network formation which is thus a product of the concatenation of cascaded PTMs. This leads to a formulation different from current protein synthesis models in which neural networks initially formed from these individual synaptic PTM-dependent changes is maintained by regulated positive feedback maintains. One such positive feedback mechanism is ‘cryptic rehearsal’ typically referred to as ‘noise’ or ‘spontaneous’ activity. This activity is in fact not random or spontaneous but determined in a stochastic sense by the past history of activation of the nerve cell. To prevent promiscuous network formation, the regulated positive feedback maintains the altered state given specific decay kinetics for the PTM. The up or down state of individual synapses actually exists in an infinite number of intermediate states, never fully ‘up', nor fully ‘down.' The networks formed from these uncertain synapses are therefore metastable. A particular memory is also multiply represented by a ‘degenerate code’ so that should loss of a subset of representations occur, erasure can be protected against. This mechanism also solves the flexibility–stability problem by positing that the brain eschews synaptic stability having its own uncertainty principle that allows retrieval from a probabilistic network, so that a retrieved memory can be represented by a selection of components from an essentially infinite number of networks. The network so formed, that is the retrieval, thus emerges from a hierarchy of connectionistic probabilities. The relation of this new theory of memory network formation to current and potential computational implementations will benefit by its unusual point of initiation: deep concerns about the molecular substrates of information storage.
影响因子：
3.7
作者：
Izhikevich, EM;Gally, JA;Edelman, GM
通讯作者：
Edelman, GM