GABA IN THE INFERIOR COLLICULUS PLAYS A CRITICAL ROLE IN CONTROL OF AUDIOGENIC-SEIZURES

Previous studies have implicated a decreased efficacy of GABA as an im portant defect subserving the audiogenic seizures of the genetically e pilepsy-prone rat (GEPR-9). The inferior colliculus (IC) is a critical site for audiogenic seizure (AGS) initiation, and the pontine reticul ar formation (PRF) is implicated in the propagation of AGS and in othe r generalized seizure models. The present study observed that microinj ection of baclofen, a GABA-B receptor agonist, into IC protects agains t AGS, and blockade of the breakdown of endogenous GABA by gabaculine, a GABA transaminase inhibitor, increased GABA levels and blocked AGS susceptibility in the GEPR-9. Microinjection of baclofen or gabaculine into the PRF reduced AGS severity, but the doses required were consid erably greater and the degree of anticonvulsant effect was less. Uptak e of [H-3]GABA into GEPR-9 synaptosomes from the IC is significantly i ncreased as compared to normal, which could contribute to the diminish ed effectiveness of GABA in the GEPR-9. Previous studies indicate that GABA-A receptor agonists block AGS with IC microinjection, and recent data indicate that blockade of GABA uptake in this nucleus significan tly reduced AGS severity. These data taken together strongly support t he critical importance of the defect in GABA function in the IC in mod ulating susceptibility to audiogenic seizure initiation in the GEPR-9.