Herpes 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.
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