ONTOGENIC FEATURES OF AUDIOGENIC-SEIZURE SUSCEPTIBILITY INDUCED IN IMMATURE RATS BY NOISE

Although numerous models are currently used for systematic study of the mechanisms of epileptogenesis in mature brain, few animal models have been developed that allow similar explorations in the developing nervous system. One experimental model of epilepsy supports a premise that perinatal experience can lead to eventual seizure susceptibility, however. Audiogenic seizure (AGS) susceptibility can be induced during a critical developmental period in normal mice by auditory deprivation and therefore by cochlear trauma. We studied the developmental parameters that affect success of both induction and testing of AGS-susceptibility in the rat. Intense high-frequency noise exposure was used as the traumatizing agent. The Wistar rat strain used is inherently seizure-resistant because in > 400 trials, untreated rats have never exhibited susceptibility at any age. Although single prolonged exposures to high-intensity noise were administered to groups of rats at ages between postnatal days (PNDs) 12 and 36, PND 14 was the age when exposure was most likely to result in eventual seizure susceptibility. Furthermore, duration of initial exposure on PND 14 determined the rate of susceptibility when measured 2 weeks later. Accordingly, we noted that single noise exposures at an intensity of 125 dB and ranging between 6 and 10 min in duration induced susceptibility in 100% of rats tested on PND 28; nonetheless, seizures among the rats exposed for 8 min were the most severe. Typically, these seizures began as wild running attacks and were followed by tonic/clonic convulsions. In a third study, we noted that a rat's maturation at the time of testing influenced the rate of susceptibility, regardless of whether the rat had been exposed for 2.5, 4, or 8 min on PND 14. In this regard, PND 28 ontogenetically appeared to be the age of greatest inherent susceptibility. Susceptibility decreased between PND 28 and 36 but remained stable thereafter into adulthood. The age of onset of susceptibility depended (inversely) on the duration of original exposure, not on maturation. Nonetheless, wild running seizure responses are not observed in fewer than 2 days after initial exposure, and tonic/clonic convulsions emerged in not fewer than 3 days. The data suggest there are at least two critically sensitive periods in genesis of AGS susceptibility, one that is specific for induction of susceptibility (PND 14) and one specific for its expression (PND 28). Together, these data strongly support a view that both experiential and maturational factors combine predictably to shape the individual rat's prognosis at specific ages.