Genetic threshold hypothesis of neocortical spike‐and‐wave discharges in the rat: An animal model of petit mal epilepsy

Abstract

Neocortical high-voltage spike-and-wave discharges (HVS) in the rat are an animal model of petit mal epilepsy. Genetic analysis of total duration of HVS (s/12 hr) in reciprocal F1 and F2 hybrids of F344 and BN rats indicated that the phenotypic variability of HVS cannot be explained by a simple, monogenic Mendelian model. Biometrical analysis suggested the presence of additive, dominance, and sex-linked-epistatic effects, buffering maternal influence, and heterosis. High correlation was observed between average duration (s/episode) and frequency of occurrence of spike-and-wave episodes (n/12 hr) in parental and segregating generations, indicating that common genes affect both duration and frequency of the spike-and-wave pattern. We propose that both genetic and developmental-environmental factors control an underlying quantitative variable, which, above a certain threshold level, precipitates HVS discharges. These findings, together with the recent availability of rat DNA markers for total genome mapping, pave the way to the identification of genes that control the susceptibility of the brain to spike-and-wave discharges.

Spike–wave discharges in adult Sprague–Dawley rats and their implications for animal models of temporal lobe epilepsy

“…Similar to previous reports [42–44], SWDs appeared to vary with the environment of animals. In previous studies environmental influences did not include housing during early life (although development has been suggested to play a role; [44]).…”

“…In previous studies environmental influences did not include housing during early life (although development has been suggested to play a role; [44]). Therefore, it is notable that we report here a potential facilitatory effect of housing, especially early in life, on SWDs.…”

Methods of automated absence seizure detection, interference by stimulation, and possibilities for prediction in genetic absence models

“…HVS, large amplitude sharp spindles, mimic SWDs, although not all included HVS would unambiguously classify as SWDs, since the spikes of the HVS might be less sharp and the waves were sometimes missing. 16 6-8 months old rats (Fischer 344 and Brown Norway strains) were used to develop and train the system, as well as their F1 and F2 descendents, and back-crosses with the parental strains for its evaluation and subsequent quantitative genetic analyses of the HVS (Vadász et al, 1995). An artificial neural network was used, which should be first properly trained before its generated the desired output of the test data set.…”

“…for genetic analyses of absence epilepsy Vadász et al, 1995;Gauguier et al, 2004). These long lasting recordings are also necessary for the study of long term drug effects and epileptogenesis , for chronic drug studies (D'Amore et al, 2014), for the study of circadian rhythms of SWDs and the consequences of their shifts (Smyk et al, 2012).…”

Scaling Brain Size, Keeping Timing: Evolutionary Preservation of Brain Rhythms

“…For example, thalamocortical μ rhythm is sex and strain dependent in both rats and mice (Peeters et al, 1992; Marescaux et al, 1992; Vadász et al, 1995; Noebels 2003). A study of REM sleep in numerous strains of mice indicated the presence of a gene with a major effect on theta frequency, which could explain more than 80% of the total variability among strains (Franken et al, 1998).…”