REMOVAL OF THE INFERIOR OLIVE ABOLISHES MYOCLONIC SEIZURES ASSOCIATEDWITH A LOSS OF OLIVARY SEROTONIN

Several lines of clinical evidence suggest that myoclonus is caused by a reduction of serotonin in the brain and hyperactivity of the inferi or olive. We determined whether a change in serotonin content within t he olivocerebellar system accompanied a predisposition to myoclonus an d investigated the necessity of the inferior olive for a myoclonic sei zure. The experiments employed the genetically epilepsy-prone rat that exhibits a profound myoclonic seizure in response to an auditory stim ulus. We found that these animals demonstrated a significant reduction in the serotonergic innervation of the inferior olive without a signi ficant change in the serotonergic innervation at any other level of th e olivocerebellar circuit. The deficit in olivary serotonin was verifi ed physiologically and pharmacologically by a reduced sensitivity of t he generically epilepsy prone rat to the tremorogenic effect of harmal ine, which is known to produce tremor through a mechanism that require s serotonergic innervation of the inferior olive. We quantified the ti ming of the myoclonic seizure of the genetically epilepsy-prone rat an d found that its large amplitude 2-6 Hz clonus was always preceded by 9-10 Hz tremor that was synchronized among limbs. Ablation of the infe rior olive by 3-acetylpyridine abolished the myoclonic seizure. The sp ecificity of the deficit in olivary serotonin, the timing of the seizu re, and the demonstration of the necessity of the inferior olive for m yoclonus suggest that pathological inferior olivary activity contribut es to the genesis of a myoclonic seizure. (C) 1997 IBRO.