Acute lipopolysaccharide exposure facilitates epileptiform activity via enhanced excitatory synaptic transmission and neuronal excitability in vitro

Abstract

Fei Gao,1,2 Zhiqiang Liu,3 Wei Ren,3 Wen Jiang1 1Department of Neurology, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, People’s Republic of China; 2Department of Neurology, First Affiliated Hospital of Xi’an Medical University, Xi’an 710077, People’s Republic of China; 3College of Life Sciences, Shaanxi Normal University, Xi’an 710062, People’s Republic of China Abstract: Growing evidence indicates brain inflammation has been involved in the genesis of seizures. However, the direct effect of acute inflammation on neuronal circuits is not well known. Lipopolysaccharide (LPS) has been used extensively to stimulate brain inflammatory responses both in vivo and in vitro. Here, we observed the contribution of inflammation induced by 10 μg/mL LPS to the excitability of neuronal circuits in acute hippocampal slices. When slices were incubated with LPS for 30 minutes, significant increased concentration of tumor necrosis factor α and interleukin 1β were detected by enzyme-linked immunosorbent assay. In electrophysiological recordings, we found that frequency of epileptiform discharges and spikes per burst increased 30 minutes after LPS application. LPS enhanced evoked excitatory postsynaptic currents but did not modify evoked inhibitory postsynaptic currents. In addition, exposure to LPS enhanced the excitability of CA1 pyramidal neurons, as demonstrated by a decrease in rheobase and an increase in action potential frequency elicited by depolarizing current injection. Our observations suggest that acute inflammation induced by LPS facilitates epileptiform activity in vitro and that enhancement of excitatory synaptic transmission and neuronal excitability may contribute to this facilitation. These results may provide new clues for treating seizures associated with brain inflammatory disease. Keywords: lipopolysaccharide, hippocampus, inflammation, epileptiform activity, synaptic transmission, neuronal excitability