Abstracts

RATIONALE: The Frings audiogenic seizure-susceptible mouse is a genetic model for sensory-evoked reflex seizures. The audiogenic seizure phenotype in the Frings mouse is the result of a single spontaneous mutation producing a premature stop codon in [italic]mass1[/italic]. Recently, longer isoforms encoded by alternate transcripts have been identified as a new member of the very large G protein-coupled receptor subfamily. The present study tests the hypothesis that the [italic]mass1[/italic] mutation alters intrinsic neuroexcitability in Frings mice and in a congenic strain with the Frings [italic]mass1[/italic] alleles placed on the C57BL/6 background.
METHODS: Regional neuroexcitability was assessed by determining transcorneal electroconvulsive thresholds for minimal clonic (60Hz, 0.2s), maximal tonic (60Hz, 0.2s) and psychomotor-partial (6Hz, 3.0s) seizures. The thresholds for each electroconvulsive seizure test were measured in both genders of Frings, SWR/J, C57BL/6 and congenic (Frings x C57BL/6) mice. Statistical significance between groups was determined using Probit analysis.
RESULTS: For each of the electroconvulsive seizure tests, results obtained from Frings mice were compared to those from SWR/J mice, and results from C57BL/6 mice were compared to those from congenic mice. In general, the C57BL/6 and congenic mice exhibited higher electroconvulsive thresholds than Frings and SWR/J mice, and male mice displayed higher thresholds than female mice within each strain. In the maximal electroconvulsive seizure test, the congenic mice exhibited a significantly lower seizure threshold compared to the C57BL/6 mice (females, p[lt]0.05; males, p[lt]0.01), and the Frings female mice were lower compared to the SWR/J female mice (p[lt]0.01). For the psychomotor-partial electroconvulsive seizure test, the congenic female mice displayed a lower threshold compared to C57BL/6 female mice (p[lt]0.01). The minimal electroconvulsive seizure test did not reveal a difference between any of the groups evaluated. A decrease in the ratio for maximal to minimal electroconvulsive seizure thresholds for Frings and congenic mice compared to SWR/J and C57BL/6 mice was also observed.
CONCLUSIONS: The [italic]mass1[/italic] mutation in the Frings and congenic mice lowered the threshold for maximal electroconvulsive seizures demonstrating an effect on neuroexcitablility within the brainstem. The only evidence for lowered thresholds in the forebrain was observed in the congenic female mice. These results are consistent with the observations that audiogenic seizures predominately involve brainstem structures. The decreased ratio for maximal to minimal electroconvulsive thresholds observed in the Frings and congenic mice suggests a lowered resistance to seizure spread.
[Supported by: NIH Grant NS38616-01 (LJP,HSW), HHMI (LJP), NIH Contract N01NS42311 NINDS (HSW,KSW), AFPE (BDK).]