NEC Seminar: Friday, August 23, 9:00 AM
Speaker: Jiaxin Zhou
Advisor: Prof. D. Durand
Title: The Effect of 4-AP-induced Interictal Epileptiform Discharges (IEDs) on Synaptic Plasticity
Abstract: Individuals with epilepsy commonly contend with a spectrum of cognitive co-morbidities, with memory impairment being particularly prevalent. Despite ongoing research into the origins of these memory issues, a significant factor identified is the prevalence of interictal epileptiform discharges (IEDs). These discharges primarily occur in critical brain regions such as the cortex and hippocampus and can propagate non-synaptically. Both human intracortical studies and in-vivo rodent experiments consistently demonstrate a strong association between IED prevalence and memory impairment. However, the cellular and physiological mechanisms underlying this relationship remain poorly understood, partly due to the predominant reliance on behavioral markers in existing studies. To address this gap, our in-vitro mouse model study investigates the hypothesis that IEDs induce synaptic downregulation and depression within the hippocampus. We employed 4-Aminopyridine (4-AP) to induce epileptiform activity and measured changes in excitatory evoked postsynaptic potentials (EPSPs) from the CA1 stratum radiatum, evoked by single-pulse stimulation of the Schaffer collaterals. The observed changes in EPSP were used to determine long-term depression or potentiation.Our findings demonstrate a significant correlation between 4-AP-induced IEDs and synaptic depression over time, evidenced by an average decrease of 82.31 ± 5.42% in EPSP slope following the generation of IEDs. Moreover, retrospective analysis revealed that lower spiking IED frequencies are associated with more pronounced synaptic downregulation. This synaptic downregulation appears capable of propagating through a complete gap in tissue, concomitantly with the IEDs, suggesting that the effects can extend non-synaptically.
This in-vitro exploration seeks to assess the impact of IEDs on synaptic plasticity directly and to provide a foundational model for understanding memory dysfunction in epilepsy. Our study contributes to the underexplored area of targeting IEDs as a potential therapeutic approach for memory impairment, a condition frequently endured by individuals with epilepsy.