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 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.
Wankerl
Katharina
K
Human Cortical Physiology and Motor Control Laboratory, Department of Neurology, University of Wuerzburg, D-97080 Wuerzburg, Germany.
Weise
David
D
Gentner
Reinhard
R
Rumpf
Jost-Julian
JJ
Classen
Joseph
J
D000328:Adult; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000502:physiology*; D003915:Dextromethorphan / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D019054:Evoked Potentials, Motor / Q000187:drug effects / Q000502:physiology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D006801:Humans; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D036881:Long-Term Synaptic Depression / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009044:Motor Cortex / Q000187:drug effects / Q000502:physiology; D009119:Muscle Contraction / Q000502:physiology; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D009553:Nimodipine / Q000494:pharmacology; D011712:Pyramidal Tracts / Q000187:drug effects / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D050781:Transcranial Magnetic Stimulation
D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D018691:Excitatory Amino Acid Antagonists; D009553:Nimodipine; D003915:Dextromethorphan
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