title: Differential Regulation of Human Paired Associative Stimulation-Induced and Theta-Burst Stimulation-Induced Plasticity by L-type and T-type Ca2+ Channels.
abstract: Activity-dependent changes of postsynaptic Ca2+-concentration are influenced by a variety of different Ca2+-channels and play an important role in synaptic plasticity. Paired associative stimulation (PAS) and theta-burst stimulation (TBS) are noninvasive magnetic stimulation protocols used in human subjects to induce lasting corticospinal excitability changes that have been likened to synaptic long-term potentiation and long-term depression. To better characterize the Ca2+-related physiological mechanisms underlying PAS- and TBS-induced plasticity, we examined the impact of different Ca2+-sources. PAS-induced facilitation of corticospinal excitability was blocked by NMDA-receptor blocker dextromethorphan (DXM) and L-type voltage gated Ca2+ channels (VGCC) blocker nimodipine (NDP), but turned into depression by T-type VGCC blocker ethosuximide (ESM). Although, surprisingly, static corticospinal excitability was increased by the combination of DXM and NDP, PAS-induced facilitation was blocked. TBS-induced facilitation of corticospinal excitability, which has previously been shown to be turned into depression by L-type VGCC blocker NDP (Wankerl K, Weise D, Gentner R, Rumpf J, Classen J. 2010. 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. J Neurosci. 30(18):6197-6204.), was blocked, but not reverted, by T-type VGCC blocker ESM. The different patterns of Ca2+-channel modulation of PAS- and TBS-induced plasticity may point to an important role of backpropagating action potentials in PAS-induced plasticity, similar as in spike-timing dependent synaptic plasticity, and to a requirement of dendritic Ca2+-dependent spikes in TBS-induced plasticity.
authors.affiliation: Department of Neurology, University of Leipzig, Liebigstr. 20, 04103 Leipzig, Germany.
authors.forename: David
authors.initials: D
authors.lastname: Weise
authors.affiliation: Department of Neurology, University of Leipzig, Liebigstr. 20, 04103 Leipzig, Germany.
authors.forename: Jakob
authors.initials: J
authors.lastname: Mann
authors.affiliation: Department of Neurology, University of Leipzig, Liebigstr. 20, 04103 Leipzig, Germany.
authors.forename: Jost-Julian
authors.initials: JJ
authors.lastname: Rumpf
authors.affiliation: Institute of Physiology, University of Leipzig, Liebigstr. 27, 04103 Leipzig, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Hallermann
authors.affiliation: Department of Neurology, University of Leipzig, Liebigstr. 20, 04103 Leipzig, Germany.
authors.forename: Joseph
authors.initials: J
authors.lastname: Classen
mesh_terms: D000293:Adolescent; D000328:Adult; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D020747:Calcium Channels, T-Type / Q000378:metabolism*; D004576:Electromyography; D019054:Evoked Potentials, Motor / Q000187:drug effects / Q000502:physiology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D006225:Hand / Q000502:physiology; D006801:Humans; D008297:Male; D009044:Motor Cortex / Q000187:drug effects / Q000502:physiology*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000502:physiology; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D011712:Pyramidal Tracts / Q000187:drug effects / Q000378:metabolism; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors / Q000378:metabolism; D050781:Transcranial Magnetic Stimulation / Q000379:methods*; D055815:Young Adult
chemical_list: D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D020747:Calcium Channels, T-Type; D018691:Excitatory Amino Acid Antagonists; D018091:Receptors, AMPA
keywords: calcium channels; human motor cortex; paired associative stimulation; synaptic plasticity; theta-burst stimulation