问题描述
有实验依据吗？
这个得问问 Anki 的老祖宗啦！SuperMemo 在这方面有研究，我这里搬运并翻译（由于专业术语太多了，我只能粗浅的机翻+润色）一下：
Structural and molecular mechanisms of the spacing effect
间隔效应的结构与分子机理
From supermemo.guru
This article by Dr Piotr Wozniak is part of SuperMemo Guru series on memory, learning, creativity, and problem solving.
Outline
New memories form as new synaptic connections. When memories are in use, they may undergo stabilization by adding AMPA receptors. When memories are not in use, new dendritic filopodia may scout their surroundings for new synaptic targets. Frequent use of memory relies on fast AMPA transmission. Infrequent use may allow of filopodial growth, and allow of the activation of NMDA receptors that would (1) stabilize the synapse (adding new AMPA receptors), and (2) stabilize the dendritic arbor (incl. retraction of filopodia). Memory disuse may result in a failure of postsynaptic activation and forgetting by interference due to a takeover of the activation target by newly stabilized dendritic spines, or the reuse of NMDA-based silent synapses.
大纲
新的记忆形成为新的突触连接。使用记忆时，可能会通过添加AMPA受体来使其稳定。当不使用记忆时，新的树突状丝状伪足可能会在周围寻找新的突触靶标。频繁使用记忆依赖于快速AMPA传输。偶尔使用可能会导致丝状伪足生长，并会激活NMDA受体，从而使（1）稳定突触（添加新的AMPA受体），和（2）稳定树突状分支（包括缩回丝状伪足）。记忆的废止可能导致突触后激活失败，并且由于新稳定的树突棘接管了激活目标，或者由于基于NMDA的沉默突触的重复使用而导致的干扰而导致遗忘。
Concept network
- the brain is a concept network
- spacing effect is necessary for the efficient optimization of memory that underlies intelligence
- a concept neuron corresponds with a single meaningful idea
- a neural link between two concepts represents a single memory
- a concept neuron is activated by a set of dendritic inputs forming the activation pattern
- in terms of spaced repetition: a combination of inputs corresponds with the decoded question. Activation corresponds with the answer
- the neuronal activity is suppressed by inhibitory input that serves activation selectivity
- a depolarization signal sent out via the axon corresponds with the activation of a concept in memory
概念网
- 大脑是一个概念网络
- 间隔效应对于有效地优化智能基础的记忆是必需的
- 一个概念神经元对应一个有意义的想法
- 两个概念之间的神经联系代表单个记忆
- 一个概念神经元通过形成激活图案的一组树突输入激活
- 就间隔重复而言：输入的组合与解码后的问题相对应。激活与答案相对应
- 神经元活性被抑制性输入抑制，该抑制性输入起到激活选择性的作用
- 通过轴突发出的去极化信号对应于存储器中概念的激活
Dendritic filopodia
树突丝状伪足
New memories
- axonal-dendritic overlap favors developing coherent memories in semantic proximity (see: Axonal-dendritic overlap favors coherence and creativity)
- formation of new dendritic spines is equivalent to building new memories in a hierarchical structure
新的记忆
- 轴突-树突重叠有利于在语义上接近发展相干记忆（请参阅：轴突-树突重叠有利于连贯性和创造力）
- 新的树突棘的形成等同于在分层结构中建立新的记忆
Fast transmission
- filopodial growth would be kept in check by fast AMPA transmission (and halted or reversed by nearby NMDA currents in stabilization)
- fast transmission keeps a dendritic arbor relatively inert on the assumption that good use needs little change
快速传输
- AMPA的快速传播将阻止丝状伪足的生长（并通过稳定的附近NMDA电流阻止或逆转）
- 快速传输使树突分支保持相对惰性，前提是良好的使用几乎不需要改变
Post-synaptic inactivity
- filopodial growth should be accelerated by low postsynaptic activity (see: Dendritic arbors undergo branching followed by stabilization)
- long periods of postsynaptic inactivity result in the growth of new dendritic filopodia in the vicinity of an active axon
- glutamate release from active axons stimulates filapodial growth via mGluR receptor
- filipodia scout the neural environment in search of attractive axonal targets. Conceptually this means that concepts seek relevant activations by other concepts
- rich filopodial growth may result in a drop in memory retrievability
- new filopodia may contribute to forgetting via interference by establishing new synaptic connections
突触后不活动
- 突触后活性低应加速丝状伪足的生长（请参阅：树突状树突先分支然后稳定）
- 长时间的突触后不活动导致活跃的轴突附近新的树突丝状伪足的生长
- 活性轴突释放出的谷氨酸盐通过mGluR受体刺激了腓肠肌的生长
- 丝状伪足搜寻神经环境以寻找有吸引力的轴突靶标。从概念上讲，这意味着概念寻求其他概念的相关激活
- 丰富的丝状伪足生长可能导致记忆可检索性下降
- 新的丝状伪足可能通过建立新的突触连接而通过干扰而导致遗忘
Stabilization
- high filopodial interference would assist the activation of NMDA receptors and stabilization of memory
- filopodial retraction should be accelerated by the stabilization of the adjacent synapses in the same dendritic arbor (see: Stabilization of dendritic spines leads to shrinkage of inactive spines)
稳定化
- 高丝状伪足干扰将有助于NMDA受体的激活和记忆的稳定
- 应通过稳定同一树突状分支中相邻突触的速度来加速丝状伪足缩回（请参阅：树突状棘突的稳定导致无活动性棘突的萎缩）
NMDA and AMPA
门冬氨酸和氨甲基膦酸
New memories
- newly formed synapses and silent synapses are primarily populated by NMDA receptors
- synapse stabilization adds AMPA receptors to the PSD
新的记忆
- 新形成的突触和沉默突触主要由NMDA受体组成
- 突触稳定化为PSD增加AMPA受体
Fast transmission
- fast AMPA transmission leads to hyperpolarization that prevents the activation of NMDA receptors
- without NMDA calcium currents, stabilization is negligible, impact on inactive filipodia is less pronounced
快速传输
- 快速AMPA传输导致超极化，阻止NMDA受体的激活
- 没有NMDA钙电流，稳定度可忽略不计，对非活动性纤维脂病的影响不太明显
Post-synaptic inactivity
- sprouting of nearby filopodia builds up a reservoir of AMPA receptors that can be remobilized for the purpose of stabilization
- phosphorylation of AMPA receptor may contribute to memory retrievability, fast transmission, and potential activation of NMDA receptors
- NMDA-induced currents (in a stabilized synapse), in conjunction with the activation of mGluR receptor would result in retracting unused filipodia
- retraction of filopodia could allow of a transfer mobilized AMPARs to the stabilized synapse, which would enhance the spacing effect
突触后不活动
- 附近丝状伪足的发芽建立了AMPA受体库，可将其转移以达到稳定的目的
- AMPA受体的磷酸化可能有助于记忆可恢复性，快速传播以及NMDA受体的潜在激活
- NMDA诱导的电流（处于稳定的突触中），与mGluR受体的激活相结合，将导致收回未使用的纤维脂蛋白
- 丝状足的退缩可以使动员的AMPARs转移至稳定的突触，这将增强间隔效应
Stabilization
- co-activation of the axon and the postsynaptic neuron may result in NMDA calcium currents that stabilize the synapse
- activation of the NMDA receptors would be more likely in case of interference from proximal filopodia
- NMDA-induced currents would favor incorporation of new AMPAR units (adding to molecular stabilization)
- increase in stability means facilitated AMPA transmission and slower growth of filopodia (see: AMPA receptors stabilize the dendritic branch)
稳定化
- 轴突和突触后神经元的共同激活可能导致稳定突触的NMDA钙电流
- 在近端丝状伪足干扰的情况下，NMDA受体的激活更有可能
- NMDA诱导的电流将有利于引入新的AMPAR单元（增加了分子稳定性）
- 稳定性的增加意味着促进AMPA的传播和丝状伪足的生长减慢（请参阅：AMPA受体稳定树突状分支）
Forgetting
- forgetting would occur primarily via interference
- post-synaptic inactivity may result in a takeover of a concept neuron by new patterns based on the maturation of new dendritic spines
- prolonged disuse of the synapse can also lead to memory decay by molecular and cellular changes (e.g. phosphorylation status, subunit structure, AMPA endocytosis, cytoskeletal stability, etc.)
- prolonged disuse may result in the ultimate loss of the dendritic spine
遗忘
- 遗忘主要是通过干扰发生的
- 突触后的不活动可能导致基于新的树突棘成熟的新模式接管概念神经元
- 长时间不使用突触也可通过分子和细胞变化（例如磷酸化状态，亚基结构，AMPA内吞作用，细胞骨架稳定性等）导致记忆衰退。
- 长时间不使用可能会导致树突状脊柱最终消失
有关更多信息，请参见：遗忘机制
For more see: Mechanism of forgetting
History
历史
The above reasoning is derived from the statistical properties of memory as described in the Neurostatistical Model of Memory. The data has largely been obtained by employing a spaced repetition algorithm. Statistical properties of memory make it possible to hypothesize about the interaction of the individual molecular, cellular and neural phenomena that occur while wiring the concept network of the brain in the course of development and learning. The molecular and structural interpretation is largely mine, and is based on well-documented facts of neuroscience. Some of the hypothetical assumptions are pretty bold. My boldness is justified by the idea that any falsifiable model is better than an absence of models.
上面的推论是根据记忆的神经统计模型中描述的记忆的统计特性得出的。数据很大程度上是通过采用间隔重复算法获得的。记忆的统计特性使我们有可能对在发展和学习过程中连接大脑概念网络时发生的各个分子，细胞和神经现象的相互作用进行假设。分子和结构的解释很大程度上是我的，并且是基于神经科学的有据可查的事实。一些假设假设非常大胆。我的大胆之处在于，任何可证伪的模型都比没有模型更好。
- I proposed the two component model of long-term memory in 1988 (for details see: Two components of memory)
- 我在1988年提出了长期记忆的两个成分模型（有关详细信息，请参阅：记忆的两个成分）
- in Optimization of learning in 1990, I hypothesized for the first time about molecular correlates of the memory model. At that time, structural changes seemed unlikely as I was not aware of the speed of the growth of filopodia. However, glutamate, increase in the number of receptors and the calcium signal were already included in the hypothetical model
- 在1990年的“优化学习”中，我首次假设了记忆模型的分子相关性。那时，结构变化似乎不太可能，因为我不了解丝状伪足的生长速度。但是，假设模型中已经包括了谷氨酸盐，受体数量的增加和钙信号。
- in Economics of learning in 1995, in co-operation with Dr Edward Gorzelanczyk, we refined the model by hypothesizing about the role of NMDA receptors, mGluR, protein phosphorylation, and the possibility of exposing new receptors on the post-synaptic membrane
- 在1995年的《学习经济学》中，我们与Edward Gorzelanczyk博士合作，通过假设NMDA受体，mGluR，蛋白质磷酸化的作用以及在突触后膜上暴露新受体的可能性，对模型进行了完善。
- in the new millennium the evidence for dendritic dynamics kept mounting and it became obvious that structural changes are necessary when forming new memories. In retrospect, the whole idea of a dynamic concept network seems obvious and necessary. The reliance on solely molecular changes might be energetically prudent, but computationally infeasible
- 在新的千年中，树突动力学的证据越来越多，很明显在形成新的记忆时必须进行结构改变。回想起来，动态概念网络的整个想法似乎很明显并且是必要的。仅依靠分子变化可能会非常谨慎，但在计算上是不可行的
- in 2017, mounting structural evidence resulted in my proposition of the two-component model of memory stability
- 在2017年，越来越多的结构证据导致我提出了记忆稳定性的两部分模型
- in 2019, I concluded that the sprouting of new filopodia might be the main cause of forgetting via interference. This would make them a good candidate for memory retrievability. All we need is a good link between the activation of NMDA receptors and the retraction of nearby filipodia. That mechanism would be a solid candidate for the neural explanation of the spacing effect.
- 在2019年，我得出结论认为，新丝状伪足的发芽可能是通过干扰而遗忘的主要原因。这将使它们成为记忆可恢复性的良好候选者。我们需要的是NMDA受体的激活与附近纤维质疏松的撤退之间的良好联系。该机制将是对间距效应进行神经解释的可靠候选者。
- the presented model was compiled in March 2020, and should be seen as the best fit between biology and statistics as seen via the inspirational lens of spaced repetition.
- 本文提出的模型于2020年3月编制，从间隔重复的鼓舞人心的角度来看，应该被视为生物学和统计学之间的最佳拟合。
Verification
Caution! The presented model of the spacing effect is hypothetical. It can still include errors, or need a major revision. However, its evolution over the last 30 years seems to indicate a good convergence with data. If you are aware of biological data that contradicts the model or is hard to explain in its light, please let me know.
验证
警告！提出的间距效应模型是假设的。它仍然可以包含错误，或者需要进行重大修订。但是，它在过去30年的发展似乎表明与数据的良好融合。如果您知道与该模型相抵触或难以解释的生物学数据，请告知我。