Research ReportTransmeningeal muscimol can prevent focal EEG seizures in the rat neocortex without stopping multineuronal activity in the treated area

Muscimol has potent antiepileptic efficacy after transmeningeal administration in animals. However, it is unknown whether this compound stops local neuronal firing at concentrations that prevent seizures. The purpose of this study was to test the hypothesis that epidurally administered muscimol can prevent acetylcholine (Ach)-induced focal seizures in the rat neocortex without causing cessation of multineuronal activity. Rats were chronically implanted with a modified epidural cup over the right frontal cortex, with microelectrodes positioned underneath the cup. In each postsurgical experimental day, either saline or 0.005-, 0.05-, 0.5- or 5.0-mM muscimol was delivered through the cup, followed by a 20-min monitoring of the multineuronal activity and the subsequent delivery of Ach in the same way. Saline and muscimol pretreatment in the concentration range of 0.005-0.05 mM did not prevent EEG seizures. In contrast, 0.5-mM muscimol reduced the average EEG Seizure Duration Ratio value from 0.30 ± 0.04 to 0. At this muscimol concentration, the average baseline multineuronal firing rate of 10.9 ± 4.4 spikes/s did not change significantly throughout the 20-min pretreatment. Muscimol at 5.0 mM also prevented seizures, but decreased significantly the baseline multineuronal firing rate of 7.0 ± 1.8 to 3.7 ± 0.9 spikes/s in the last 10 min of pretreatment. These data indicate that transmeningeal muscimol in a submillimolar concentration range can prevent focal neocortical seizures without stopping multineuronal activity in the treated area, and thus this treatment is unlikely to interrupt local physiological functions.

Graphical Abstract279Research Highlights► Transmeningeal acetylcholine (Ach) induces seizures in the rat neocortex. ► Transmeningeal muscimol can prevent Ach-induced neocortical seizures in rats. ► Transmeningeal muscimol can prevent Ach-seizures in submillimolar concentrations. ► Submillimolar transmeningeal muscimol does not stop local multineuronal firing. ► Transmeningeal muscimol can be antiepileptic without interrupting local functions.