Synaptic mechanisms that contribute to human memory consolidation remain largely unexplored. Consolidation critically relies on sleep. During slow wave sleep, neurons exhibit characteristic membrane potential oscillations known as UP and DOWN states. Coupling of memory reactivation to these slow oscillations promotes consolidation, though the underlying mechanisms remain elusive. Here, we performed axonal and multineuron patch-clamp recordings in acute human brain slices, obtained from neurosurgeries, to show that sleep-like UP and DOWN states modulate axonal action potentials and temporarily enhance synaptic transmission between neocortical pyramidal neurons. Synaptic enhancement by UP and DOWN state sequences facilitates recruitment of postsynaptic action potentials, which in turn results in long-term stabilization of synaptic strength. In contrast, synapses undergo lasting depression if presynaptic neurons fail to recruit postsynaptic action potentials. Our study offers a mechanistic explanation for how coupling of neural activity to slow waves can cause synaptic consolidation, with potential implications for brain stimulation strategies targeting memory performance.

有助于人类记忆巩固的突触机制在很大程度上仍未得到探索。巩固严重依赖于睡眠。在慢波睡眠期间，神经元表现出特征性的膜电位振荡，称为 UP 和 DOWN 状态。记忆再激活与这些缓慢振荡的耦合促进了巩固，尽管潜在机制仍然难以捉摸。在这里，我们在从神经外科手术获得的急性人脑切片中进行了轴突和多神经元膜片钳记录，以表明类似睡眠的 UP 和 DOWN 状态调节轴突动作电位并暂时增强新皮层锥体神经元之间的突触传递。UP 和 DOWN 状态序列的突触增强促进了突触后动作电位的募集，这反过来又导致突触强度的长期稳定。相反，如果突触前神经元无法募集突触后动作电位，突触会经历持久的抑制。我们的研究为神经活动与慢波的耦合如何导致突触巩固提供了机制解释，对针对记忆表现的大脑刺激策略具有潜在影响。