美国哥伦比亚大学Attila Losonczy等研究人员合作发现，抑制性可塑性支持海马体中的重放泛化。相关论文于2024年9月3日在线发表在《自然—神经科学》杂志上。

研究人员表示，记忆巩固将近期经历融入长期记忆中。这一过程需要重放学习序列，尽管这些序列的内容仍存在争议。最近的研究表明，重放的统计特征与经历的统计特征有所不同：那些在经历中显著的刺激可能会被招募或抑制在尖波-涟波中。

研究人员发现，这一现象可以通过一种在抑制性突触处的赫布时序依赖性可塑性规则来简明且生物学上合理地解释。通过使用三种抽象层次的模型——漏积分-发放模型、生物物理详细模型和抽象二进制模型——研究人员展示了这一规则如何实现高效的泛化，并对完整和扰动的抑制性动态对网络动态和认知的影响做出了具体预测。

最后，研究人员使用光遗传学技术在清醒行为小鼠中人工植入非泛化的表征，发现这些表征在尖波-涟波期间也会积累抑制，从而实验性地验证了其模型的一个主要预测。该研究概述了突触层面与认知层面之间的潜在直接联系，对正常学习和神经疾病都有重要意义。

附：英文原文

Title: Inhibitory plasticity supports replay generalization in the hippocampus

Author: Liao, Zhenrui, Terada, Satoshi, Raikov, Ivan Georgiev, Hadjiabadi, Darian, Szoboszlay, Miklos, Soltesz, Ivan, Losonczy, Attila

Issue&Volume: 2024-09-03

Abstract: Memory consolidation assimilates recent experiences into long-term memory. This process requires the replay of learned sequences, although the content of these sequences remains controversial. Recent work has shown that the statistics of replay deviate from those of experience: stimuli that are experientially salient may be either recruited or suppressed from sharp-wave ripples. In this study, we found that this phenomenon can be explained parsimoniously and biologically plausibly by a Hebbian spike-time-dependent plasticity rule at inhibitory synapses. Using models at three levels of abstraction—leaky integrate-and-fire, biophysically detailed and abstract binary—we show that this rule enables efficient generalization, and we make specific predictions about the consequences of intact and perturbed inhibitory dynamics for network dynamics and cognition. Finally, we use optogenetics to artificially implant non-generalizable representations into the network in awake behaving mice, and we find that these representations also accumulate inhibition during sharp-wave ripples, experimentally validating a major prediction of our model. Our work outlines a potential direct link between the synaptic and cognitive levels of memory consolidation, with implications for both normal learning and neurological disease. The study of neural plasticity has focused on excitatory neural connections, but inhibitory connections can also change. Learning at inhibitory synapses may support high-level cognitive phenomena, such as selecting information for memory storage.

DOI: 10.1038/s41593-024-01745-w

Source: https://www.nature.com/articles/s41593-024-01745-w