Department of Neuroscience, Columbia University, New York, NY, USA.
Mortimer B. Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY, USA.
Nat Neurosci. 2024 Oct;27(10):1987-1998. doi: 10.1038/s41593-024-01745-w. Epub 2024 Sep 3.
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.
记忆巩固将近期经验整合到长期记忆中。这个过程需要重放学习序列，但这些序列的内容仍然存在争议。最近的研究表明，重放的统计数据与经验不同：在经历中突出的刺激可能被招募或从尖峰波涟漪中抑制。在这项研究中，我们发现通过抑制性突触的赫布式尖峰时间依赖性可塑性规则，可以简洁地、在生物学上合理地解释这种现象。使用三种抽象水平的模型——漏电积分器和放电、生物物理详细和抽象二进制——我们表明，该规则可以实现有效的泛化，并且我们对完整和干扰抑制动力学对网络动力学和认知的影响做出了具体预测。最后，我们使用光遗传学在清醒活动的小鼠中人为地将不可泛化的表示植入网络中，并且我们发现这些表示在尖峰波涟漪中也积累抑制，实验验证了我们模型的主要预测。我们的工作概述了记忆巩固的突触和认知水平之间的潜在直接联系，对正常学习和神经疾病都有影响。
