ROLE OF THE FASTIGIAL NUCLEUS IN GENERALIZED SEIZURES AS DEMONSTRATEDBY GABA AGONIST MICROINJECTIONS

The cerebellum is electrically and metabolically active during seizure s. Numerous studies have also shown that cerebellar electrical stimula tion and lesions of the cerebellar cortex or nuclei influence seizure threshold, but there are significant contradictions, with different ef fects observed even in investigations using the same species and simil ar seizure types and experimental manipulations. Discrete intracerebra l microinjection of neuroactive agents has been used to characterize t he way in which other brain regions control seizures, but has not been applied to the cerebellar systems. This approach has advantages becau se effects are restricted to specific receptors and spare passing axon s; experimental variables also can be simply specified and reproduced. We used this method to characterize the role of the cerebellar nuclei 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 com pared with different doses of the GABA(A) agonist piperidine-4-sulfoni c acid and the GABA(B) agonist (-)baclofen (Bf). Soon after injection, the animals were ataxic. After 4 min, seizures were induced by timed continuous intravenous (i.v.) bicuculline (BIC) infusion. Bath GABA ag onists produced significant reductions in myoclonic, clonic, and tonic seizure thresholds. Injections just dorsal or anterior to this nucleu s and bilateral dentate (lateral) nucleus injections had little effect on seizures. These results demonstrate that the cerebellar system doe s control seizures, but does not provide support for the early concept that cerebellar stimulation and systemic phenytoin block seizures thr ough inhibition of cerebellar nuclei secondary to Purkinje cell activa tion.