Pontine reticular formation neurons exhibit a premature and precipitous increase in acoustic responses prior to audiogenic seizures in genetically epilepsy-prone rats

Abstract

The genetically epilepsy-prone rat (GEPR-9) exhibits elevated seizure sensitivity and audiogenic seizures (AGS). The pontine reticular formation (PRF) is implicated in the neuronal network for AGS in the GEPR-9. The present study examined PRF neuronal firing and convulsive behavior simultaneously in the GEPR-9. Chronically implanted microwire electrodes in PRF allowed single neuronal responses and behavior to be examined in freely-moving rats. PRF neurons in the GEPR-9 exhibit precipitous intensity-evoked increases at a significantly lower (approx. 15 dB SPL) intensity than normal Sprague-Dawley rats. PRF neurons in the GEPR-9 also exhibit increased auditory response latencies. At the onset of AGS (wild running) the firing rate of PRF neurons increased, and the rate of PRF firing increased dramatically as the tonic phase of the seizure began. During post-ictal depression the rate of PRF neuronal firing slowed, gradually returning to normal. This pattern of PRF periseizural neuronal firing changes differ dramatically in pattern and temporal characteristics from those previously observed in inferior colliculus (IC). The IC serves as the AGS initiation site. IC neurons show extensive firing increases prior to and during the initial wild running, silence during the tonic and post-ictal phases, and gradual recovery of responses thereafter. The changes in PRF neuronal firing pattern suggest that the PRF may play a major role in the generation of the tonic phase of AGS. The premature onset of the precipitous rise in PRF neuronal firing suggests that the influence of the IC on PRF neurons may be magnified in association with AGS susceptibility. The PRF neuronal firing increases observed in the present study coupled with previous observation of AGS blockade by PRF microinjections in the GEPR-9 further support an important role of the PRF in the propagation of AGS in the GEPR-9. The mechanisms of PRF firing elevation may also be relevant in other seizure models in which the brain-stem reticular formation is implicated.