SEIZURES AND PROTOONCOGENE EXPRESSION OF FOS IN THE BRAIN OF ADULT GENETICALLY EPILEPSY-PRONE RATS

The mechanisms and brain circuitry that render genetically epilepsy-pr one rats (GEPRs) susceptible to acoustically induced seizures are not completely known. The present study explores the neuroanatomy of acous tically induced seizures by immunohistochemical analysis of the proto- oncoprotein fos after intense acoustic stimulation (AS) with and witho ut seizures. Acoustic stimulation induced tonic convulsions in GEPR-9s , but not in control rats. Locations of brain nuclei showing fos-like immunoreactive (FLI) neurons following AS with and without seizures we re mapped. Semiquantitative methods were used to compare FLI neuron nu merical densities in AS control rats and GEPRs. Many brain areas exhib ited profound FLI in AS control rats and GEPRs. Unexpectedly, the coch lear nuclei and the central nucleus of the inferior colliculi (ICc), b oth of which are requisite for AGS initiation, exhibited a diminished fos expression in animals having seizures compared to AS controls. In contrast, GEPRs displayed a significant increase in FLI neurons within the dorsal cortex of the IC (ICd) compared to AS controls. This findi ng may suggest a seizure-related amplification of the auditory signal between the ICc and the ICd. Other nuclei, known to be involved in aud itory transmission (i.e., superior olivary complex; trapezoid nucleus; dorsal nucleus of the lateral lemniscus, DNLL), did not Show differen tial FLI densities between seizure and AS control animals. In contrast , seizure-induced FLI was observed in many nonauditory brain nuclei. O f particular interest was the identification of an intensely labeled n ucleus in the GEPR. This nucleus resides in the most posterior and dor sal-lateral part of the pedunculopontine tegmental nucleus-pars compac ta (PPTn-pc) immediately adjacent to the DNLL and extends posteriorly into the superior lateral subnucleus of the lateral parabrachial area (SLPBn). Therefore, we have tentatively termed this nucleus the PPSLPB n. The PPSLPBn lies in a region previously described as a mesencephali c locomotor region and a suspected functional involvement of this nucl eus in display of seizure activity is under investigation. Other brain stem nuclei showing differential fos expression between GEPRs and AS control rats are also described. (C) 1997 Academic Press.