双时间反馈环的互锁增强记忆随机性和持久性的鲁棒性
Interlinked Dual-Time Feedback Loops can Enhance Robustness to Stochasticity and Persistence of Memory
摘要：
多个相互关联的正反馈回路塑造了各种生化系统的刺激反应，如细胞周期或细胞内钙释放。最近的研究与简化的模型已经确定了两个优点耦合快，慢反馈回路。即，该双时间结构能够实现快速响应，同时增强响应的抵抗性和对刺激噪声的双稳态。我们现在发现，另外：1）双时间结构赋予抵抗由于分子数波动引起的内部噪声的能力，以及2）具有改变的耦合的模型变体，其更好地代表一些特定的系统，共享所有上述优点。我们开发了一个类似的快速自激活循环耦合到一个缓慢的循环，这最低限度地代表了正反馈，可能是必不可少的长期突触增强（LTP）模型。快速响应和抗噪声的优点延续到这个模型。根据经验，LTP在约1小时内对逆转产生抗性。该模型表明，这种阻力可能是由于参与正反馈的突触激酶数量增加所致。
英文摘要：
Multiple interlinked positive feedback loops shape the stimulus responses of various biochemical systems, such as the cell cycle or intracellular calcium release. Recent studies with simplified models have identified two advantages of coupling fast and slow feedback loops. Namely, this dual-time structure enables a fast response while enhancing resistances of responses and bistability to stimulus noise. We now find that in addition: 1) the dual-time structure confers resistance to internal noise due to molecule number fluctuations, and 2) model variants with altered coupling, which better represent some specific systems, share all the above advantages. We develop a similar bistable model with a fast autoactivation loop coupled to a slow loop, which minimally represents positive feedback that may be essential for long-term synaptic potentiation (LTP). The advantages of fast response and noise resistance carry over to this model. Empirically, LTP develops resistance to reversal over ~1 h. The model suggests this resistance may result from increased amounts of synaptic kinases involved in positive feedback.
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