Elsevier

Neuroscience

Volume 82, Issue 3, 24 October 1997, Pages 879-897
Neuroscience

Removal of the inferior olive abolishes myoclonic seizures associated with a loss of olivary serotonin

https://doi.org/10.1016/S0306-4522(97)00297-2Get rights and content
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Abstract

Several lines of clinical evidence suggest that myoclonus is caused by a reduction of serotonin in the brain and hyperactivity of the inferior olive. We determined whether a change in serotonin content within the olivocerebellar system accompanied a predisposition to myoclonus and investigated the necessity of the inferior olive for a myoclonic seizure. The experiments employed the genetically epilepsy-prone rat that exhibits a profound myoclonic seizure in response to an auditory stimulus. We found that these animals demonstrated a significant reduction in the serotonergic innervation of the inferior olive without a significant change in the serotonergic innervation at any other level of the olivocerebellar circuit. The deficit in olivary serotonin was verified physiologically and pharmacologically by a reduced sensitivity of the genetically epilepsy-prone rat to the tremorogenic effect of harmaline, which is known to produce tremor through a mechanism that requires serotonergic innervation of the inferior olive. We quantified the timing of the myoclonic seizure of the genetically epilepsy-prone rat and 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 inferior olive by 3-acetylpyridine abolished the myoclonic seizure.

The specificity of the deficit in olivary serotonin, the timing of the seizure, and the demonstration of the necessity of the inferior olive for myoclonus suggest that pathological inferior olivary activity contributes to the genesis of a myoclonic seizure.

Keywords

olivocerebellar system
movement disorder
timing
tremor
genetically epilepsy prone rat
oscillation

Abbreviations

3-AP, 3-acetylpyridine
ABC, avidin–biotin–peroxidase
ARS, audiogenic response score
BSA, bovine serum albumin
cMAO, caudal medial accessory olive
DAO, dorsal accessory olive
DCN, deep cerebellar nuclei
GEPR, genetically epilepsy-prone rat
MAO, medial accessory olive
NSE, neuron-specific enolase
PB, phosphate buffer
PO, principal olive

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