Hippocampal sharp‐wave ripples (SWRs) support the reactivation of memory representations, relaying information to neocortex during “offline” and sleep‐dependent memory consolidation. While blockade of NMDA receptors (NMDAR) is known to affect both learning and subsequent consolidation, the specific contributions of NMDAR activation to SWR‐associated activity remain unclear. Here, we combine biophysical modeling with in vivo local field potential (LFP) and unit recording to quantify changes in SWR dynamics following inactivation of NMDAR. In a biophysical model of CA3‐CA1 SWR activity, we find that NMDAR removal leads to reduced SWR density, but spares SWR properties such as duration, cell recruitment and ripple frequency. These predictions are confirmed by experiments in which NMDAR‐mediated transmission in rats was inhibited using three different NMDAR antagonists, while recording dorsal CA1 LFP. In the model, loss of NMDAR‐mediated conductances also induced a reduction in the proportion of cell pairs that co‐activate significantly above chance across multiple events. Again, this prediction is corroborated by dorsal CA1 single‐unit recordings, where the NMDAR blocker ketamine disrupted correlated spiking during SWR. Our results are consistent with a framework in which NMDA receptors both promote activation of SWR events and organize SWR‐associated spiking content. This suggests that, while SWR are short‐lived events emerging in fast excitatory‐inhibitory networks, slower network components including NMDAR‐mediated currents contribute to ripple density and promote consistency in the spiking content across ripples, underpinning mechanisms for fine‐tuning of memory consolidation processes.

中文翻译：

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NMDA受体促进海马尖波波纹和CA1锥体细胞的相关共活性

海马尖波波纹 (SWR) 支持记忆表征的重新激活，在“离线”和依赖睡眠的记忆巩固期间将信息传递给新皮层。虽然已知 NMDA 受体 (NMDAR) 的阻断会影响学习和随后的巩固，但 NMDAR 激活对 SWR 相关活动的具体贡献仍不清楚。在这里，我们将生物物理建模与体内局部场电位 (LFP) 和单位记录相结合，以量化 NMDAR 失活后 SWR 动力学的变化。在 CA3-CA1 SWR 活动的生物物理模型中，我们发现去除 NMDAR 会导致 SWR 密度降低，但会保留 SWR 属性，例如持续时间、细胞募集和纹波频率。这些预测得到了实验的证实，实验证实了使用三种不同的 NMDAR 拮抗剂抑制大鼠 NMDAR 介导的传播，同时记录背侧 CA1 LFP。在该模型中，NMDAR 介导的电导损失也导致细胞对的比例减少，这些细胞对的共同激活显着高于多个事件的机会。同样，这一预测得到了背部 CA1 单单元记录的证实，其中 NMDAR 阻滞剂氯胺酮在 SWR 期间破坏了相关的尖峰。我们的结果与一个框架一致，其中 NMDA 受体既促进 SWR 事件的激活，又组织 SWR 相关的尖峰内容。这表明，虽然 SWR 是在快速兴奋抑制网络中出现的短暂事件，但