L-type voltage-gated Ca2+ channels: a single molecular switch for long-term potentiation/long-term depression-like plasticity and activity-dependent metaplasticity in humans

The ability of synapses to undergo persistent activity-dependent potentiation or depression [long-term potentiation (LTP)/long-term depression (LTD)] may be profoundly altered by previous neuronal activity. Although natural neuronal activity can be experimentally manipulated in vivo, very little is...

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Bibliographic Details
Published in:The Journal of neuroscience 2010-05, Vol.30 (18), p.6197-6204
Main Authors: Wankerl, Katharina, Weise, David, Gentner, Reinhard, Rumpf, Jost-Julian, Classen, Joseph
Format: Article
Language:English
Subjects:
Adult
Calcium Channel Blockers - pharmacology
Calcium Channels, L-Type - drug effects
Calcium Channels, L-Type - physiology
Dextromethorphan - pharmacology
Dose-Response Relationship, Drug
Drug Interactions
Evoked Potentials, Motor - drug effects
Evoked Potentials, Motor - physiology
Excitatory Amino Acid Antagonists - pharmacology
Female
Humans
Long-Term Potentiation - drug effects
Long-Term Potentiation - physiology
Long-Term Synaptic Depression - drug effects
Long-Term Synaptic Depression - physiology
Male
Motor Cortex - drug effects
Motor Cortex - physiology
Muscle Contraction - physiology
Neuronal Plasticity - drug effects
Neuronal Plasticity - physiology
Nimodipine - pharmacology
Pyramidal Tracts - drug effects
Pyramidal Tracts - physiology
Synaptic Transmission - drug effects
Synaptic Transmission - physiology
Transcranial Magnetic Stimulation
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Summary:The ability of synapses to undergo persistent activity-dependent potentiation or depression [long-term potentiation (LTP)/long-term depression (LTD)] may be profoundly altered by previous neuronal activity. Although natural neuronal activity can be experimentally manipulated in vivo, very little is known about the in vivo physiological mechanisms involved in regulating this metaplasticity in models of LTP/LTD. To examine whether Ca(2+) signaling may influence metaplasticity in vivo in humans, we used continuous theta burst stimulation (cTBS) (Huang et al., 2005), a noninvasive novel repetitive magnetic stimulation protocol known to induce persistent alterations of corticospinal excitability whose polarity is changed by previous voluntary motor activity. When directed to the naive motor cortex, cTBS induced long-lasting potentiation of corticospinal excitability, but depression under the influence of nimodipine (NDP), an L-type voltage-gated Ca(2+) channel (L-VGCC) antagonist. Both aftereffects were blocked by dextromethorphan, an NMDA receptor antagonist, supporting the notion that these bidirectional cTBS-induced alterations of corticospinal excitability map onto LTP and LTD as observed in animal studies. A short period of voluntary contraction and a small dose of NDP were each ineffective in blocking the cTBS-induced potentiation. However, when both interventions were combined, a depression was induced, and the magnitude of this depression increased with the dose of NDP. These findings suggest that Ca(2+) dynamics determine the polarity of LTP/LTD-like changes in vivo. L-VGCCs may act as molecular switches mediating metaplasticity induced by endogenous neuronal activation.
ISSN:0270-6474
1529-2401
DOI:10.1523/jneurosci.4673-09.2010