Aberrant neuronal responsiveness in the genetically epilepsy-prone rat: acoustic responses and influences of the central nucleus upon the external nucleus of inferior colliculus

Abstract

The inferior colliculus (IC) central nucleus (ICc), is critical for audiogenic seizure (AGS) initiation in the genetically epilepsy-prone rat (GEPR). The ICc lacks direct motor outputs but sends a major projection to the external nucleus of IC (ICx), which does project to the sensorimotor integration nuclei within the AGS neuronal network. The present study compared acoustic responses of ICx neurons in the GEPR and normal anesthetized rat and evaluated whether the GEPR exhibits functional abnormalities in the pathway from ICc to ICx. There is a significantly greater incidence of sustained repetitive response patterns to the acoustic stimulus in GEPR ICx neurons (75%) than in normal ICx neurons (24%). Following unilateral microinjection of N-methyl- d-aspartate (NMDA) into the contralateral ICc, acoustically-evoked ICx excitation and inhibition were each increased in normal animals, which is consistent with the mixed projections previously reported in this pathway and observed with electrical stimulation in the present study. The NMDA-induced ICx firing increase may be relevant to AGS, since, in previous studies, bilateral focal microinjection of NMDA into the ICc induced AGS susceptibility in normal rats [23]. However, the incidence and degree of the ICx neuronal response changes after NMDA microinjection was not abnormal in the GEPR. These data suggest that the hyperresponsiveness of ICx neurons may not involve abnormal transmission between the ICc and ICx, despite the elevated ICx neuronal responses to acoustic stimuli. However, the ICx hyperresponsivess of the GEPR, which is likely due to the known decrease in effectiveness of GABA-mediated inhibition in GEPR neurons, may be a major mechanism subserving the critical role that this structure plays in the AGS network.