Unraveling acetylcholine impact on human cortical plasticity.

Editor's Note: These short, critical reviews of recent papers in the Journal, written exclusively by graduate students or postdoctoral fellows, are intended to summarize the important findings of the paper and provide additional insight and commentary. For more information on the format and purpose of the Journal Club, please see Review of Grundey et al. In recent years, a growing number of studies on humans have used repetitive transcranial magnetic stimulation (rTMS) techniques to induce and examine plasticity in the primary motor cortex (M1). This plasticity is reflected by long-term changes in motor-evoked potential (MEP) amplitudes elicited by single-pulse TMS over M1 (after-effects; Ziemann et al., 2008). The techniques include paired associative stimulation (PAS), which consists of TMS delivered over M1 after electrical stimulation of nerves in the contralateral wrist. If TMS is delivered 25 ms after nerve stimulation (PAS 25), it induces a long-term increase in MEP size; if it is delivered 10 ms after nerve stimulation (PAS 10), it reduces MEP size (Stefan et al., 2000). Since PAS involves repetitive activation of sensorimotor circuits and since the direction of after-effects strictly depends on the specific interstimu-lus intervals used, PAS is considered to elicit a Hebbian form of heterotopic spike timing-dependent plasticity (Stefan et al., 2000; Zi-emann et al., 2008). Another experimental approach used to elicit cortical plasticity is transcranial direct current stimulation (TDCS). When the anode is placed over M1 and the cathode over the contralateral frontal pole (anodal TDCS), MEPs increase in size; when polarity is inverted (cathodal TDCS), MEPs decrease in size (Nitsche and Paulus, 2000). TDCS works through whole-brain polarization and is believed to induce depolar-ization or hyperpolarization of the resting membrane potential (Nitsche and Paulus, 2000). Both PAS-and TDCS-induced after-effects are believed to reflect long-term poten-tiation (LTP)-and long-term depression (LTD)-like mechanisms (Nitsche and Paulus, 2000; Stefan et al., 2000; Ziemann et al., 2008). Recent studies have investigated the possibility of boosting PAS-and TDCS-induced plasticity using drugs, including those that act on cholinergic transmission (Kuo et al., 2007; Thirugnanasambandam et al., 2011; Grundey et al., 2012). Acetyl-choline (ACh) may play an important role in attention, learning, and memory by modulating cortical LTP and LTD (Lavio-lette and van der Kooy, 2004; Changeux, 2010). After enhancing global cholinergic transmission with rivastigmine, a cholin-esterase inhibitor, Kuo et al. (2007) found that anodal TDCS failed to increase MEPs, whereas PAS 25 elicited long-term MEP enhancement. More recently, Thirug-nanasambandam et …