Selection for spontaneous or priming-induced audiogenic seizure susceptibility in mice.

Abstract

Four lines of mice were selectively bred from a heterogeneous foundation stock for audiogenic seizure prone (SP), priming prone (PP), moderately priming prone (MPP) and seizure resistant (SR). Significant changes in proportions of animals showing the desired phenotypes were found after 2 generations of selection, indicating involvement of genetic components in these behavioral characteristics. Although response to selection for spontaneous seizure proneness was rapid, initial seizure risk is not controlled by a single recessive gene. The effects of tympanic membrane perforation on development of seizure susceptibility in these 4 selected lines were investigated. The method is highly effective in inducing seizure susceptibility in the PP mice and the SR mice, but not so effective for the SP and the MPP lines. Spontaneous and priming-induced seizure susceptibility could be due to the development of hyperreactivity in centripetal auditory structures brought about by the reduction of auditory input. The phenotypic difference between the PP and the SR lines could be due to differences in their cochlear susceptibility to stimulation damage but a qualitatively different mechanism is involved in the MPP line.