A possible role of olivary gap-junctions in the generation of physiological and pathological tremors

Loewenstein, Yonatan

doi:10.1038/sj.mp.4000994

Cited by 14 publications

(11 citation statements)

References 14 publications

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“…There is extensive evidence implicating the IO in the origins of harmaline tremors (Llinás and Volkind, 1973;de Montigny and Lamarre, 1973). It seems natural to assume that the electrical coupling of IO neurons plays a role in coordinating strong volleys of afferent excitation to the cerebellum, which in turn lead to synchronous tremor-inducing output to motor structures (Loewenstein, 2002). Indeed, that is what we expected.…”

Section: Discussionsupporting

confidence: 62%

Rhythmicity without Synchrony in the Electrically Uncoupled Inferior Olive

et al. 2002

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Neurons of the inferior olivary nucleus (IO) form the climbing fibers that excite Purkinje cells of the cerebellar cortex. IO neurons are electrically coupled through gap junctions, and they generate synchronous, subthreshold oscillations of membrane potential at approximately 5-10 Hz. Experimental and theoretical studies have suggested that both the rhythmicity and synchrony of IO neurons require electrical coupling. We recorded from pairs of IO neurons in slices of mouse brainstem in vitro. Most pairs of neurons from wild-type (WT) mice were electrically coupled, but coupling was rare and weak between neurons of knock-out (KO) mice for connexin36, a neuronal gap junction protein. IO cells in both WT and KO mice generated rhythmic membrane fluctuations of similar frequency and amplitude. Oscillations in neighboring pairs of WT neurons were strongly synchronized, whereas the oscillations of KO pairs were uncorrelated. Spontaneous oscillations in KO neurons were not blocked by tetrodotoxin. Spontaneously oscillating neurons of both WT and KO mice generated occasional action potentials in phase with their membrane rhythms, but only the action potentials of WT neuron pairs were synchronous. Harmaline, a beta-carboline derivative thought to induce tremor by facilitating rhythmogenesis in the IO, was injected systemically into WT and KO mice. Harmaline-induced tremors were robust and indistinguishable in the two genotypes, suggesting that gap junction-mediated synchrony does not play a role in harmaline-induced tremor. We conclude that electrical coupling is not necessary for the generation of spontaneous subthreshold oscillations in single IO neurons, but that coupling can serve to synchronize rhythmic activity among IO neurons.

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Section: Discussionsupporting

confidence: 62%

Rhythmicity without Synchrony in the Electrically Uncoupled Inferior Olive

et al. 2002

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“…Alcohol ingestion decreases the amplitude, although typically not the frequency of postural tremors; its effect is however frequently short-lived and may cause rebound worsening upon wearing off [110]. The mechanism of action by which alcohol exerts its effects is unclear, but a direct effect on the inferior olivary nuclei and/or effects on GABA transmission are suspected [111], [112]. Studies have shown that ethanol activates GABA-A, glycine, and nicotinic acetylcholine receptors, and that it inhibits N-methyl-D-aspartate (NMDA) glutamate receptors [113].…”

Section: - Alcohol Use In Patients With Movement Disorders: Essentiamentioning

confidence: 99%

Substance Abuse and Movement Disorders: Complex Interactions and Comorbidities

Deik¹,

Saunders‐Pullman²,

Luciano³

2012

CDAR

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The relationship between movement disorders and substance abuse which we previously reviewed are updated. We examine these relationships bidirectionally with focus on drugs of abuse which cause movement disorders, as well as primary movement disorders that are associated with use and abuse of alcohol and dopaminergic medications. First, we review the movement disorders that may develop from the acute use or withdrawal of frequent drugs of abuse, including alcohol, cocaine, heroin, amphetamine and methcathinone. We then comment on the interaction between alcoholism and alcohol-responsive movement disorders, such as essential tremor and myoclonus-dystonia. Lastly, we discuss the potential for abuse of antiparkinsonian dopaminergic agents in patients with Parkinson’s disease (PD).

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“…Harmaline, a β‐carboline alkaloid, can induce tremor in laboratory animals that is similar to that seen in ET, through its actions on the inferior olivary (IO) nuclei (Deuschl & Elble 2000). IO neurons, which project to the cerebellar cortex through climbing fibers and to the deep nuclei of the cerebellum, have a natural tendency to oscillate in a synchronous fashion at a frequency of 4–10 Hz (Loewenstein 2002). This oscillatory activity may be due to electrical coupling of IO neurons through dendrodendritic gap junctions that are modulated by nearby γ‐aminobutyric acid (GABA) synapses.…”

Section: Essential Tremormentioning

confidence: 99%

“…The harmaline animal model of ET has thus identified the IO as the most likely single location of the proposed central oscillator. Alcohol may exert its suppressive effect on tremor by directly acting on the IO, perhaps by the blocking gap junctions that permit oscillatory activity or effecting calcium currents (Loewenstein 2002). 1‐octanol, which compared with ethanol reduces harmaline‐induced tremor at doses much lower than intoxicating doses (Wilms et al .…”

Section: Essential Tremormentioning

confidence: 99%

REVIEW: Movement disorders and alcohol misuse

Hess

Saunders‐Pullman

2006

Addiction Biology

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Many movement disorders, including tics, chorea, tremor, myoclonus and parkinsonism, may result from substance abuse. However, alcohol in particular is associated in a more complex manner with two specific movement disorders, essential tremor (ET) and myoclonus-dystonia (M-D). In this review we discuss the comorbidity of alcohol abuse in both ET and M-D, the ameliorative effects of alcohol in both diseases, and review the data evaluating alcohol abuse secondary to self-medication. We also discuss shared pathophysiologic mechanisms in the understanding of both of these disorders, as the elucidation of the mechanisms by which alcohol exerts its effects may lead to novel therapeutic approaches.

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A possible role of olivary gap-junctions in the generation of physiological and pathological tremors

Cited by 14 publications

References 14 publications

Rhythmicity without Synchrony in the Electrically Uncoupled Inferior Olive

Rhythmicity without Synchrony in the Electrically Uncoupled Inferior Olive

Substance Abuse and Movement Disorders: Complex Interactions and Comorbidities

REVIEW: Movement disorders and alcohol misuse

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