Mechanisms of deafferentation-induced plasticity in human motor cortex.
Deafferentation induces rapid plastic changes in the cerebral cortex, probably via unmasking of pre-existent connections. Several mechanisms may contribute, such as changes in neuronal membrane excitability, removal of local inhibition, or various forms of short- or long-term synaptic plasticity. To understand further the mechanisms involved in cortical plasticity, we tested the effects of CNS-active drugs in a plasticity model, in which forearm ischemic nerve block (INB) was combined with low-frequency repetitive transcranial magnetic stimulation (rTMS) of the deafferented human motor cortex. rTMS was used to upregulate the plastic changes caused by INB. We studied six healthy subjects. In two control sessions without drug application, INB plus rTMS increased the motor-evoked potential (MEP) size and decreased intracortical inhibition (ICI) measured with single- and paired-pulse TMS in the biceps brachii muscle proximal to INB. A single oral dose of the benzodiazepine lorazepam (2 mg) or the voltage-gated Na+ and Ca2+ channel blocker lamotrigine (300 mg) abolished these changes. The NMDA receptor blocker dextromethorphan (150 mg) suppressed the reduction in ICI but not the increase in MEP size. With sleep deprivation, used to eliminate sedation as a major factor of these drug effects, INB plus rTMS induced changes similar to that seen in the control sessions. The findings suggest that (1) the INB plus rTMS-induced increase in MEP size involves rapid removal of GABA-related cortical inhibition and short-term changes in synaptic efficacy dependent on Na+ or Ca2+ channels and that (2) the long-lasting (>60 min) reduction in ICI is related to long-term potentiation-like mechanisms given its duration and the involvement of NMDA receptor activation.
Human Cortical Physiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892-1428, USA.
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Ziemann
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Hallett
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Cohen
D000328:Adult; D000344:Afferent Pathways / Q000502:physiology; D002121:Calcium Channel Blockers / Q000627:therapeutic use; D003714:Denervation; D003864:Depression, Chemical; D003915:Dextromethorphan / Q000627:therapeutic use; D018691:Excitatory Amino Acid Antagonists / Q000627:therapeutic use*; D018755:GABA Agonists / Q000627:therapeutic use*; D006801:Humans; D015640:Ion Channel Gating; D000077213:Lamotrigine; D008140:Lorazepam / Q000627:therapeutic use; D008297:Male; D009044:Motor Cortex / Q000502:physiology*; D009433:Neural Inhibition / Q000187:drug effects; D009473:Neuronal Plasticity / Q000502:physiology*; D026941:Sodium Channel Blockers; D014227:Triazines / Q000627:therapeutic use
D002121:Calcium Channel Blockers; D018691:Excitatory Amino Acid Antagonists; D018755:GABA Agonists; D026941:Sodium Channel Blockers; D014227:Triazines; D003915:Dextromethorphan; D008140:Lorazepam; D000077213:Lamotrigine