Midbrain pathways of audiogenic seizures in [formula omitted] mice

Abstract

The effects on audiogenic seizures of bilateral electrolytic lesions at levels of the inferior colliculus (IC), superior colliculus (SC), or medial geniculate body were determined for inbred DBA 2 mice. Of 88 control mice (surgical and nonsurgical), 82% displayed the full seizure syndrome when exposed to intense sound: wildrunning attacks progressed to clonic convulsions and then tonic convulsions. All remaining control animals displayed at least wild-running attacks. In 27 of 49 mice with IC-level lesions, either no seizure activity was observed or the syndrome terminated at the wild-running stage. In these mice, lesions consistently damaged the central IC nucleus (ICC) and sometimes adjacent midbrain tegmentum. In the 12 IC-lesion mice that displayed the full seizure syndrome, IC damage was generally lateral, primarily involving the external IC nucleus (ICX). In SC-lesion mice, absence of wild-running was observed in only 3 of 23 mice, but termination of seizures at wild-running or clonic stages was often seen (14 of 23 mice). Attenuation of seizure activity was correlated with damage to the deep SC and tegmentum, including the central gray. Little or no effect on audiogenic seizures was found with lesions of the dorsal SC or medial geniculate body. Analysis of the time course of components of the seizure syndrome revealed that IC-lesion mice attaining only the wild-running stage had increased latencies to onset of this behavior. In SC-lesion mice, time to onset of wild-running did not differ significantly from controls. Progression from wild-running attacks to onset of clonic convulsions was slowed by lesions at both IC and SC levels. The data indicate that the primary pathway of audiogenic seizure activity includes the ICC, deep SC, and adjacent tegmentum. Wild-running attacks appear to be mediated at the IC level, whereas progression to clonic and tonic convulsions may require more rostral levels.