Neuroscience Institute, Langone Medical Center, New York University, New York, NY 10016.
Department of Neurosurgery, Erlangen University Hospital, Friedrich Alexander University Erlangen-Nuremberg, 91054 Erlangen, Germany.
Proc Natl Acad Sci U S A. 2023 Aug 22;120(34):e2302676120. doi: 10.1073/pnas.2302676120. Epub 2023 Aug 17.
Interictal epileptiform discharges (IEDs) are transient abnormal electrophysiological events commonly observed in epilepsy patients but are also present in other neurological diseases, such as Alzheimer's disease (AD). Understanding the role IEDs have on the hippocampal circuit is important for our understanding of the cognitive deficits seen in epilepsy and AD. We characterize and compare the IEDs of human epilepsy patients from microwire hippocampal recording with those of AD transgenic mice with implanted multilayer hippocampal silicon probes. Both the local field potential features and firing patterns of pyramidal cells and interneurons were similar in the mouse and human. We found that as IEDs emerged from the CA3-1 circuits, they recruited pyramidal cells and silenced interneurons, followed by post-IED suppression. IEDs suppressed the incidence and altered the properties of physiological sharp-wave ripples, altered their physiological properties, and interfered with the replay of place field sequences in a maze. In addition, IEDs in AD mice inversely correlated with daily memory performance. Together, our work implies that IEDs may present a common and epilepsy-independent phenomenon in neurodegenerative diseases that perturbs hippocampal-cortical communication and interferes with memory.
发作间期癫痫样放电（IEDs）是一种常见于癫痫患者的短暂异常电生理事件，但也存在于其他神经疾病中，如阿尔茨海默病（AD）。了解 IEDs 在海马回电路中的作用对于我们理解癫痫和 AD 中观察到的认知缺陷很重要。我们通过微丝海马记录，对人类癫痫患者的 IEDs 进行了特征描述和比较，这些患者来自植入多层海马硅探针的 AD 转基因小鼠。在小鼠和人类中，局部场电位特征和锥体神经元及中间神经元的放电模式都很相似。我们发现，IEDs 从 CA3-1 回路中出现时，会募集锥体神经元并抑制中间神经元，随后出现 IED 后抑制。IEDs 抑制了生理快波涟漪的发生并改变了其性质，改变了它们的生理性质，并干扰了在迷宫中的位置场序列的重放。此外，AD 小鼠的 IEDs 与每日记忆表现呈负相关。总的来说，我们的工作表明，IEDs 可能是神经退行性疾病中一种共同的、与癫痫无关的现象，它扰乱了海马-皮质通讯并干扰了记忆。
