Herpes simplex virus type 1 inoculation enhances hippocampal excitability and seizure susceptibility in mice

Abstract

AbstractHerpes simplex virus type 1 (HSV‐1) is the major pathogen related to epilepsy. However, little is known about the pathogenesis of HSV‐1‐associated epilepsy. Here, we report that corneal inoculation of mice with HSV‐1 induces acute spontaneous behavioural and electrophysiological seizures and chronically increases hippocampal excitability and seizure susceptibility. In slices from infected mice, the surviving hippocampal CA3 pyramidal neurons exhibited a more depolarizing resting membrane potential concomitant with an increase in membrane input resistance. They also had a lower threshold for generating synchronized bursts and a decrease in the amplitude of afterhyperpolarization (AHP) than did controls. These results suggest that a direct change in the excitability of the hippocampal CA3 neuronal network could play an important role in facilitating the development of acute seizures and subsequent epilepsy.