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

J. P. Welsh, B. Chang, M. E. Menaker, Sue Aicher

Research output: Contribution to journalArticle

27 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)879-897
Number of pages19
JournalNeuroscience
Volume82
Issue number3
DOIs
StatePublished - Oct 24 1997
Externally publishedYes

Fingerprint

Serotonin
Seizures
Myoclonus
Epilepsy
Tremor
Harmaline
Extremities
Brain

Keywords

  • Genetically epilepsy prone rat
  • Movement disorder
  • Olivocerebellar system
  • Oscillation
  • Timing
  • Tremor

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Removal of the inferior olive abolishes myoclonic seizures associated with a loss of olivary serotonin. / Welsh, J. P.; Chang, B.; Menaker, M. E.; Aicher, Sue.

In: Neuroscience, Vol. 82, No. 3, 24.10.1997, p. 879-897.

Research output: Contribution to journalArticle

Welsh, J. P. ; Chang, B. ; Menaker, M. E. ; Aicher, Sue. / Removal of the inferior olive abolishes myoclonic seizures associated with a loss of olivary serotonin. In: Neuroscience. 1997 ; Vol. 82, No. 3. pp. 879-897.
@article{7327e3fa875544cd847600b2570e9a13,
title = "Removal of the inferior olive abolishes myoclonic seizures associated with a loss of olivary serotonin",
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 = "Genetically epilepsy prone rat, Movement disorder, Olivocerebellar system, Oscillation, Timing, Tremor",
author = "Welsh, {J. P.} and B. Chang and Menaker, {M. E.} and Sue Aicher",
year = "1997",
month = "10",
day = "24",
doi = "10.1016/S0306-4522(97)00297-2",
language = "English (US)",
volume = "82",
pages = "879--897",
journal = "Neuroscience",
issn = "0306-4522",
publisher = "Elsevier Limited",
number = "3",

}

TY - JOUR

T1 - Removal of the inferior olive abolishes myoclonic seizures associated with a loss of olivary serotonin

AU - Welsh, J. P.

AU - Chang, B.

AU - Menaker, M. E.

AU - Aicher, Sue

PY - 1997/10/24

Y1 - 1997/10/24

N2 - 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.

AB - 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.

KW - Genetically epilepsy prone rat

KW - Movement disorder

KW - Olivocerebellar system

KW - Oscillation

KW - Timing

KW - Tremor

UR - http://www.scopus.com/inward/record.url?scp=0342506486&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0342506486&partnerID=8YFLogxK

U2 - 10.1016/S0306-4522(97)00297-2

DO - 10.1016/S0306-4522(97)00297-2

M3 - Article

C2 - 9483543

AN - SCOPUS:0342506486

VL - 82

SP - 879

EP - 897

JO - Neuroscience

JF - Neuroscience

SN - 0306-4522

IS - 3

ER -