A genetic context for the study of audiogenic seizures.

Here, the genetic context for the study of audiogenic seizures is four single-gene, spontaneous mutations that occurred in the Behavior Genetics Laboratory at the University of Chicago from 1959 to 1969. Three of these increased the incidence of audiogenic seizures, and one of these decreased the incidence of audiogenic seizures. The genetics of one of these mutants is described in detail, and the effect of diet on the same mutant is also described in detail. Research on genetic and environmental effects on the cortical EEG of audiogenic seizures is reviewed; this research included two of these mutants. The cortical EEG associated with audiogenic seizures in this study was consistent with audiogenic seizures being a type of brain stem epilepsy as had been proposed by others. Also, I proposed that brain stem pathophysiology is the same regardless of the genetic or environmental pathway to audiogenic seizure susceptibility. Research is also reviewed using these mutants to determine whether or not a strain association between glutamic acid decarboxylase (GAD) activity in whole brain and susceptibility to audiogenic seizures is pleiotropic and whether or not a strain association between nucleoside triphosphatase (NTPase) activity in the granule cell layer of the dentate fascia of the hippocampus and susceptibility to audiogenic seizures is a lineal or collateral pleiotropy. Lastly, pleiotropy as an explanation for strain comorbidities in aggressive behavior and audiogenic seizures is considered. This article is part of a Special Issue entitled "Genetic and Reflex Epilepsies, Audiogenic Seizures and Strains: From Experimental Models to the Clinic".