Jw. Miller et al., ROLE OF THE FASTIGIAL NUCLEUS IN GENERALIZED SEIZURES AS DEMONSTRATEDBY GABA AGONIST MICROINJECTIONS, Epilepsia, 34(6), 1993, pp. 973-978
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.