Department of Biology, Institute for Theoretical Biology, Humboldt-Universität zu Berlin, Berlin, Germany.
Bernstein Center for Computational Neuroscience Berlin, Berlin, Germany.
J Physiol. 2024 Oct;602(19):5039-5059. doi: 10.1113/JP285671. Epub 2024 Aug 31.
Sharp wave-ripple complexes (SPW-Rs) are spontaneous oscillatory events that characterize hippocampal activity during resting periods and slow-wave sleep. SPW-Rs are related to memory consolidation - the process during which newly acquired memories are transformed into long-lasting memory traces. To test the involvement of SPW-Rs in this process, it is crucial to understand how SPW-Rs originate and propagate throughout the hippocampus. SPW-Rs can originate in CA3, and they typically spread from CA3 to CA1, but little is known about their formation within CA3. To investigate the generation and propagation of SPW-Rs in CA3, we recorded from mouse hippocampal slices using multi-electrode arrays and patch-clamp electrodes. We characterized extracellular and intracellular correlates of SPW-Rs and quantified their propagation along the pyramidal cell layer of CA3. We found that a hippocampal slice can be described by a speed and a direction of propagation of SPW-Rs. The preferred propagation direction was from CA3c (the subfield closer to the dentate gyrus) toward CA3a (the subfield at the boundary to CA2). In patch-clamp recordings from CA3 pyramidal neurons, propagation was estimated separately for excitatory and inhibitory currents associated with SPW-Rs. We found that propagation speed and direction of excitatory and inhibitory currents were correlated. The magnitude of the speed of propagation of SPW-Rs within CA3 was consistent with the speed of propagation of action potentials in axons of CA3 principal cells. KEY POINTS: Hippocampal sharp waves are considered important for memory consolidation; therefore, it is of interest to understand the mechanisms of their generation and propagation. Here, we used two different approaches to study the propagation of sharp waves in mouse CA3 in vitro: multi-electrode arrays and multiple single-cell recordings. We find a preferred direction of propagation of sharp waves from CA3c toward CA3a - both in the local field potential and in sharp wave-associated excitatory and inhibitory synaptic activity. The speed of sharp wave propagation is consistent with the speed of action potential propagation along the axons of CA3 pyramidal neurons. These new insights into the dynamics of sharp waves in the CA3 network will inform future experiments and theoretical models of sharp-wave generation mechanisms.
尖波涟漪复合波（SPW-Rs）是在静息期和慢波睡眠期间特征性地出现于海马区的自发振荡事件。SPW-Rs 与记忆巩固有关——即在这个过程中，新获得的记忆被转化为持久的记忆痕迹。为了测试 SPW-Rs 在这个过程中的参与程度，了解 SPW-Rs 如何在海马区中起源和传播是至关重要的。SPW-Rs 可以起源于 CA3，它们通常从 CA3 传播到 CA1，但关于它们在 CA3 内的形成过程知之甚少。为了研究 SPW-Rs 在 CA3 中的产生和传播，我们使用多电极阵列和膜片钳电极从小鼠海马切片中进行记录。我们描述了 SPW-Rs 的细胞外和细胞内相关特征，并量化了它们在 CA3 锥体细胞层中的传播。我们发现，一个海马切片可以用 SPW-Rs 的传播速度和方向来描述。首选的传播方向是从 CA3c（更靠近齿状回的亚区）到 CA3a（与 CA2 交界的亚区）。在 CA3 锥体神经元的膜片钳记录中，我们分别估计了与 SPW-Rs 相关的兴奋性和抑制性电流的传播速度。我们发现，兴奋性和抑制性电流的传播速度和方向是相关的。SPW-Rs 在 CA3 内传播的速度与 CA3 主细胞轴突中的动作电位传播速度一致。关键点：海马区的尖波被认为对记忆巩固很重要；因此，了解它们产生和传播的机制是很有意义的。在这里，我们使用两种不同的方法来研究体外小鼠 CA3 中尖波的传播：多电极阵列和多个单细胞记录。我们发现，从 CA3c 到 CA3a 的尖波传播存在一个首选方向——无论是在局部场电位还是在与尖波相关的兴奋性和抑制性突触活动中。尖波传播的速度与沿 CA3 锥体神经元轴突传播的动作电位速度一致。这些关于 CA3 网络中尖波动力学的新见解将为未来的尖波产生机制的实验和理论模型提供信息。
