Role of the Fastigial Nucleus in Generalized Seizures as Demonstrated by GABA Agonist Microinjections

The cerebellum is electrically and metaboli cally active during seizures. Numerous studies have also shown that cerebellar electrical stimulation and lesions of the cerebellar cortex or nuclei influence seizure thresh old, but there are significant contradictions, with different effects observed even in investigations using the same species and similar seizure types and experimental ma nipulations. Discrete intracerebral microinjection of neu roactive agents has been used to characterize the way in which other brain regions control seizures, but has not been applied to the cerebellar systems. This approach has advantages because effects are restricted to specific re ceptors and spare passing axons; experimental variables also can be simply specified and reproduced. We used this method to characterize the role of the cerebellar nu clei in seizures and to determine if observed effects could be reproduced with different agents at different doses. Effects of bilateral control microinjections in the fastigial (medial) cerebellar nucleus were compared with different doses of the GABA_A agonist piperidine-4-sulfonic acid and the GABA_B agonist (?)baclofen (Bf). Soon after in jection, the animals were ataxic. After 4 min, seizures were induced by timed continuous intravenous (i.v.) bicu culline (BIC) infusion. Both GABA agonists produced significant reductions in myoclonic, clonic, and tonic sei zure thresholds. Injections just dorsal or anterior to this nucleus and bilateral dentate (lateral) nucleus injections had little effect on seizures. These results demonstrate that the cerebellar system does control seizures, but does not provide support for the early concept that cerebellar stimulation and systemic phenytoin block seizures through inhibition of cerebellar nuclei secondary to Pur kinje cell activation.