Lithium: A switch from LTD- to LTP-like plasticity in human cortex

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• 作者：Hanna Voytovych ; Lucia Krivá ; neková ; Ulf Ziemann ; ^{u.ziemann@em.uni-frankfurt.de}
• 关键词：Lithium ; Transcranial magnetic stimulation ; Paired associative stimulation ; Long-term potentiation ; Long-term depression ; Motor cortex
• 刊名：Neuropharmacology
• 出版年：2012
• 期刊代码：33_00283908
• 类别：pha
• 出版时间：August, 2012
• 卷：63
• 期：2
• 页码：274-279
• 文件大小：236 K

摘要

Lithium, a simple cation, is the mainstay treatment of bipolar disorder. Deficient synaptic plasticity is considered one important mechanism of this disease. Lithium inhibits glycogen synthase kinase-3beta (GSK-3尾), which is involved in the regulation of synaptic plasticity. In animal preparations, inhibition of GSK-3尾 by lithium up-regulated long-term potentiation (LTP) of excitatory synapses but down-regulated long-term depression (LTD). The effects of lithium on plasticity in the human brain are unexplored. We tested the effects of a single oral dose of 900聽mg of lithium on LTP-/LTD-like plasticity in human motor cortex induced by established paired associative transcranial magnetic stimulation (PAS_LTP, PAS_LTD) protocols. We studied 10 healthy adults in a placebo-controlled double-blind randomized crossover design. PAS-induced plasticity was indexed by change in motor evoked potential amplitude recorded in a hand muscle. In the placebo session, subjects were stratified, according to the known variability of the PAS_LTP response, into PAS_LTP 鈥楲TP responders鈥?and PAS_LTP 鈥楲TD responders鈥?(n聽=聽5 each). Lithium did not affect the PAS_LTP-induced LTP-like plasticity in the 鈥楲TP responders鈥? but switched the PAS_LTP-induced LTD-like plasticity in the 鈥楲TD responders鈥?to LTP-like plasticity. In contrast, lithium had no effect on the PAS_LTD-induced LTD-like plasticity in the 鈥楲TD responders鈥? We provide first-time evidence that lithium significantly modulates brain stimulation induced plasticity in human cortex. The switch from LTD- to LTP-like plasticity is best explained by the inhibitory action of lithium on GSK-3尾. This conclusion is necessarily circumstantial because GSK-3尾 activity was not directly measured. We discuss that other important plasticity-related modes actions of lithium cannot explain our findings.