Chemical Engineering and Process Development Division, CSIR-National Chemical Laboratory, Pune 411008, India.
Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India.
Learn Mem. 2024 Jul 29;31(7). doi: 10.1101/lm.054012.124. Print 2024 Jul.
One characteristic of long-term memory is the existence of an inverted U-shaped response to increasing intervals between training sessions, and consequently, an optimal spacing that maximizes memory formation. Current models of this spacing effect focus on specific molecular components and their interactions. Here, we computationally study the underlying network architecture, in particular, the potential of motif dynamics in qualitatively capturing the spacing effect in a manner that is independent of the animal model, biomolecular components, and the timescales involved. We define a common training and test protocol, and computationally identify network topologies that can qualitatively replicate the experimentally observed characteristics of the spacing effect. For 41 motifs derived from fundamental network architectures such as autoregulation, feedback, and feedforward motifs, we tested their capacity to manifest the spacing effect in terms of an inverted U-shaped response curve, using different combinations of stimulation protocols, response metrics, and kinetic parameters. Our findings indicate that positive feedback motifs where the stimulus enhances conversion reaction in the loop replicate the spacing effect across all response metrics, while feedforward motifs exhibit a metric-specific spacing effect. For some parameter combinations, linear cascades of activation and conversion reactions were found sufficient to qualitatively exhibit spacing effect characteristics.
长期记忆的一个特点是，在训练间隔时间增加的情况下，存在着倒 U 型的反应，因此存在一个最佳的间隔时间，能够最大限度地提高记忆的形成。目前关于这种间隔效应的模型主要集中在特定的分子成分及其相互作用上。在这里，我们通过计算来研究潜在的网络结构，特别是基序动力学在定性上捕捉间隔效应的潜力，而这种方式不依赖于动物模型、生物分子成分和所涉及的时间尺度。我们定义了一个通用的训练和测试协议，并通过计算来确定能够定性地复制实验观察到的间隔效应特征的网络拓扑结构。对于来自基本网络架构（如自调节、反馈和前馈基序）的 41 个基序，我们使用不同的刺激协议、响应指标和动力学参数组合，测试了它们在倒 U 型响应曲线上表现出间隔效应的能力。我们的研究结果表明，在所有的响应指标中，刺激增强循环中转换反应的正反馈基序能够复制间隔效应，而前馈基序则表现出特定指标的间隔效应。对于某些参数组合，发现激活和转换反应的线性级联足以定性地表现出间隔效应的特征。
