TY - JOUR T1 - L-Type Voltage-Gated Ca<sup>2+</sup> Channels: A Single Molecular Switch for Long-Term Potentiation/Long-Term Depression-Like Plasticity and Activity-Dependent Metaplasticity in Humans JF - The Journal of Neuroscience JO - J. Neurosci. SP - 6197 LP - 6204 DO - 10.1523/JNEUROSCI.4673-09.2010 VL - 30 IS - 18 AU - Katharina Wankerl AU - David Weise AU - Reinhard Gentner AU - Jost-Julian Rumpf AU - Joseph Classen Y1 - 2010/05/05 UR - http://www.jneurosci.org/content/30/18/6197.abstract N2 - 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 Ca2+ 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 Ca2+ 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 Ca2+ 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. ER -