Anatomical and behavioral analyses of the inheritance of audiogenic seizures in the progeny of genetically epilepsy-prone and Sprague-Dawley rats.
Our previous studies have shown an increase in the number of GABAergic and total neurons in the inferior colliculus (IC) of the genetically epilepsy-prone rat (GEPR-9) as compared to the non-seizing Sprague-Dawley (SD) rat. To determine whether an increase in neuron number in the IC is genetically associated with seizure behavior, seizing and non-seizing offspring of GEPR-9 and SD progenitor strains were studied as well as offspring from backcrosses made with F1 and either GEPR-9 or SD rats. In addition, the ontogeny of seizure behavior was studied in seizing rats from these same backgrounds. The development of seizure behavior in GEPR-9s was shown to be dependent on age and the number of exposures to sound stimulus up until the age of 9 weeks. The F1 and F2 generations displayed different audiogenic seizure profiles than those of the two progenitor strains. In the F1 generation, the ratio of seizing to non-seizing rats was always greater than 3:1, and the distribution of seizure scores was similar for males and females. In addition, the off-spring from backcrosses made with F1 rats (high or low seizing) and GEPR-9s displayed maximal audiogenic response scores (ARS) of 9, a characteristic of the GEPR-9s used in this study. The results of these genetic studies indicate a polygenetic inheritance of this autosomal dominant trait of audiogenic seizure susceptibility. For the quantitative study of neuronal density in the IC, neurons were counted from cresyl violet-stained preparations from seizing and non-seizing F1 and F2 rats, backcrosses from different categories and age-matched SD rats. Statistically significant increases in the number of both small (70% increase) and medium-sized (14% increase) neurons occurred in the high seizing animals (ARS = 7-9) as compared to either the non-seizing F2 or SD rats. In addition, a significant increase in the number of small neurons (77% increase) occurred in the high seizing offspring of the F1 X GEPR-9 backcross as compared to that of the non-seizing offspring of the F1 X SD backcross. The data from 25 rats generated a 0.9 coefficient of linear correlation between ARS and the number of small neurons. The results from the anatomical studies suggest that the inheritance of audiogenic seizures appears to be closely linked to the increase in cell number. Therefore, the increase in cell number in the IC may be an important determinant of seizure behavior for GEPR-9s.
Ribak
C E
CE
Department of Anatomy and Neurobiology, University of California, Irvine 92717.
Roberts
R C
RC
Byun
M Y
MY
Kim
H L
HL
D000161:Acoustic Stimulation; D000367:Age Factors; D000818:Animals; D002452:Cell Count; D004827:Epilepsy / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D005260:Female; D007245:Inferior Colliculi / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D009474:Neurons / Q000145:classification; D010641:Phenotype; D051381:Rats; D011919:Rats, Inbred Strains; D011922:Rats, Mutant Strains / Q000235:genetics* / Q000502:physiology