Anti-myoclonic effect of ablation of the inferior olive

The temporal structure of myoclonus of Genetically Epilepsy Prone Rats (GEPR/3Hsd) was quantified and the effect of ablation of the inferior olive (10) was investigated. Seizures were induced by an ascending-ramp auditory stimulus (1-14 kHz, 105 dB) and measured by a non-intrusive activity monitor. The seizures of 5 GEPR/3 rats were measured before and after lesion of the IO by i.p. administration of 3-acetylpyridine, harmaline and macinamide (Llinas et al. Science, 1975). As previously described (Reigel et al., Life Sci, 1986), the seizure consisted of a running phase, clonus of the limbs, and dorsiflexion of the back, often followed by catatonia. We found that the myoclonus consisted of 2 components: a 5-10 s period of synchronous, very low amplitude limb movements at 8-12 Hz, and a subsequent 10-20 s period of large amplitude "thrashing" movements at 2-5 Hz. The neurotoxin abolished all phases of the seizure in 4 of 5 rats. By 30 d post-lesion, 2 rats had regained the seizure, but 2 were seizure-free for 3 mos, at which time their brains were removed. A Nissl stain and implant of a retrograde tracer into the cerebellar cortex revealed a complete loss of IO neurons in the seizure-free rats, and some sparing of neurons in the caudal medial accessory IO (MAO) in the 2 that regained seizures. One rat was unaffected by the lesion, and a large portion of its MAO was spared. The data indicate that the IO, the origin of the cerebellar climbing fibers, may play an important role in the induction of myoclonus and indicate a potential site of therapeutic action. Supported by the Myoclonus Research Foundation and NINDS NS-31224.