Early Sharp Waves (eSPWs) are the earliest pattern of network activity in the developing hippocampus of neonatal rodents. eSPWs were originally considered to be an immature prototype of adult SPWs, which are spontaneous top-down hippocampal events that are self-generated in the hippocampal circuitry. However, recent studies have shifted this paradigm to a bottom-up model of eSPW genesis, in which eSPWs are primarily driven by the inputs from the layers 2/3 of the medial entorhinal cortex (MEC). A hallmark of the adult SPWs is the relay of information from the CA1 hippocampus to target structures, including deep layers of the EC. Whether and how deep layers of the MEC are activated during eSPWs in the neonates remains elusive. In this study, we investigated activity in layer 5 of the MEC of neonatal rat pups during eSPWs using silicone probe recordings from the MEC and CA1 hippocampus. We found that neurons in deep and superficial layers of the MEC fire synchronously during MEC sharp potentials, and that neuronal firing in both superficial and deep layers of the MEC precedes the activation of CA1 neurons during eSPWs. Thus, the sequence of activation of CA1 hippocampal neurons and deep EC neurons during sharp waves reverses during development, from a lead of deep EC neurons during eSPWs in neonates to a lead of CA1 neurons during adult SPWs. These findings suggest another important difference in the generative mechanisms and possible functional roles of eSPWs compared to adult SPWs.

中文翻译：

---

内侧内嗅皮层浅层和深层的同步兴奋先于新生大鼠海马的早期尖波

早期尖波（eSPW）是新生啮齿动物发育中的海马体中最早的网络活动模式。 eSPW 最初被认为是成人 SPW 的不成熟原型，是海马回路中自发产生的自上而下的海马事件。然而，最近的研究已将这种范式转变为自下而上的 eSPW 起源模型，其中 eSPW 主要由内侧内嗅皮层 (MEC) 2/3 层的输入驱动。成人 SPW 的一个标志是将信息从 CA1 海马传递到目标结构，包括 EC 的深层。新生儿 eSPW 期间 MEC 深层是否被激活以及如何被激活仍然是个谜。在这项研究中，我们使用来自 MEC 和 CA1 海马的硅胶探针记录，研究了 eSPW 期间新生大鼠幼崽 MEC 第 5 层的活动。我们发现，在MEC尖电位期间，MEC深层和浅层的神经元同步放电，并且在eSPW期间，MEC浅层和深层的神经元放电先于CA1神经元的激活。因此，CA1 海马神经元和深部 EC 神经元在尖波期间的激活顺序在发育过程中发生逆转，从新生儿 eSPW 期间深部 EC 神经元的主导变为成人 SPW 期间 CA1 神经元的主导。这些发现表明，与成人 SPW 相比，eSPW 的生成机制和可能的功能作用存在另一个重要差异。