Temporal ontogeny of circuit activation prior to the onset of seizure susceptibility in EL/Suz mice.

Abstract

The EL/Suz (EL) mouse is a model of multifactorial temporal lobe epilepsy in which seizures begin around 90 days of age, but can be hastened through increased exposure to human handling. In order to better understand seizure etiology in this mouse strain relative to seizure-resistant control mice, the present study examined region-specific neuronal activation in response to non-seizure-inducing handling implemented before the onset of seizure susceptibility. Immediate-early gene (cFos) expression emerged in EL mice by postnatal day (PND) 21 in the primary motor cortex, progressed to the locus ceruleus and prefrontal cortex by PND 35, and appeared in the hippocampus and amygdala by PND 70, as mice neared the age of onset for seizure susceptibility. Thus, mirroring the pattern observed during the course of a seizure, specific brain regions were differentially recruited to a neural network for seizure predisposition before the onset of seizure susceptibility. This developmental pattern of early and transient neural activation represents an important window for the study of causal mechanisms of seizure susceptibility following exposure to environmental triggers.