期刊
出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.2302676120
关键词
Alzheimer model; sharp wave ripples; interictal epileptiform discharges; memory; replay
Interictal epileptiform discharges (IEDs) are common electrophysiological events observed in epilepsy and other neurological diseases. This study characterizes and compares IEDs in human epilepsy patients and AD transgenic mice, finding similar features and effects on the hippocampal circuit. The findings suggest that IEDs may play a role in cognitive deficits and memory interference.
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.
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