A Temporally Asymmetric Hebbian Rule Governing Plasticity in the Human Motor Cortex

Abstract

Classen. A temporally asymmetric Hebbian rule governing plasticity in the human motor cortex. J Neurophysiol 89: 2339 -2345, 2003. First published January 22, 2003 10.1152/jn.00900.2002 Synaptic plasticity is conspicuously dependent on the temporal order of the pre-and postsynaptic activity. Human motor cortical excitability can be increased by a paired associative stimulation (PAS) protocol. Here we show that it can also be decreased by minimally changing the interval between the two associative stimuli. Corticomotor excitability of the abductor pollicis brevis (APB) representation was tested before and after repetitively pairing of single right median nerve simulation with single pulse transcranial magnetic stimulation (TMS) delivered over the optimal site for activation of the contralateral APB. Following PAS, depression of TMS-evoked motor-evoked potentials (MEPs) was induced only when the median nerve stimulation preceded the TMS pulse by 10 ms, while enhancement of cortical excitability was induced using an interstimulus interval of 25 ms, suggesting an important role of the sequence of cortical events triggered by the two stimulation modalities. Experiments using F-wave studies and electrical brain stem stimulation indicated that the site of the plastic changes underlying the decrease of MEP amplitudes following PAS (10 ms) was within the motor cortex. MEP amplitudes remained depressed for approximately 90 min. The decrease of MEP amplitudes was blocked when PAS(10 ms) was performed under the influence of dextromethorphan, an N-methyl-D-aspartate-receptor antagonist, or nimodipine, an L-type voltage-gated calcium-channel antagonist. The physiological profile of the depression of human motor cortical excitability following PAS(10 ms) suggests long-term depression of synaptic efficacy to be involved. Together with earlier findings, this study suggests that strict temporal Hebbian rules govern the induction of long-term potentiation/long-term depression-like phenomena in vivo in the human primary motor cortex. I N T R O D U C T I O NActivity-dependent long-term modification of synaptic efficacy has been proposed to underlie information storage in neuronal populations. Hebb (1949) postulated that the strength of a synapse may be modulated by correlated activity of a (weak) input to a postsynaptic cell with activation of that cell, as a consequence of activity of another (strong) input to it. This principle, termed associativity, has been confirmed experimentally in numerous studies. Additionally, a stringent and surprisingly simple asymmetric temporal rule governing the direction of synaptic change has been revealed in many brain regions. With few notable exceptions (e.g., Bell et al. 1997; Egger et al. 1999; Holmgren and Zilberter 2001), it was found that associative long-term potentiation (LTP) was induced when an action potential of the postsynaptic neuron (induced by a strong input to the cell) followed the postsynaptic potential induced by a weak input. If the order of stimulation was reversed (i.e., ...

Neuromodulatory Neurotransmitters Influence LTP-Like Plasticity in Human Cortex: A Pharmaco-TMS Study

“…As a consequence, the LTP-like increase in MEP amplitude of 1.71 ± 0.05 in the PBO condition is one of the largest reported in the literature (Wolters et al, 2003;Stefan et al, 2004;Ziemann et al, 2004;Nitsche et al, 2007). Therefore, one might argue that LTP-like plasticity was saturated already under PBO conditions and could not be enhanced any further.…”

Effect of Serotonin on Paired Associative Stimulation-Induced Plasticity in the Human Motor Cortex

“…After-effects of tDCS and PAS are NMDA-and Ca 2 þ -dependent (Nitsche et al, 2003a;Stefan et al, 2002;Wolters et al, 2003). It has been shown that serotonin facilitates NMDA receptor-dependent LTP (Park et al, 2012).…”

“…Citalopram enhanced facilitatory plasticity induced by anodal tDCS and converted cathodal tDCS-induced inhibitory plasticity into facilitation . tDCS and paired associative stimulation (PAS) are non-invasive brain stimulation techniques inducing changes in cortical excitability that outlast the stimulation duration (Nitsche et al, 2003b;Paulus, 2000, 2001;Stefan et al, 2000;Wolters et al, 2003). These alterations in cortical excitability are NMDA-and Ca 2 þ -dependent (Nitsche et al, 2003a;Stefan et al, 2002;Wolters et al, 2003).…”

“…tDCS and paired associative stimulation (PAS) are non-invasive brain stimulation techniques inducing changes in cortical excitability that outlast the stimulation duration (Nitsche et al, 2003b;Paulus, 2000, 2001;Stefan et al, 2000;Wolters et al, 2003). These alterations in cortical excitability are NMDA-and Ca 2 þ -dependent (Nitsche et al, 2003a;Stefan et al, 2002;Wolters et al, 2003). tDCS induces non-focal plasticity, affecting relatively non-selectively neuronal populations beneath the large stimulation electrodes via subthreshold resting membrane potential modulation Nitsche et al, 2007;Purpura and McMurtry, 1965).…”

Deleterious Effects of a Low Amount of Ethanol on LTP-Like Plasticity in Human Cortex

“…At the systems level of human M1, LTP-like plasticity, indexed by a long-term increase in motor-evoked potential (MEP) amplitude, can be induced by paired associative stimulation (PAS LTP ) (Cooke and Bliss, 2006;Müller-Dahlhaus et al, 2010;Stefan et al, 2002;Stefan et al, 2000;Ziemann et al, 2004). This LTP-like increase in MEP amplitude shows tight similarities to cellular LTP because it is associative, input specific, and blocked by dextromethorphan, a non-competitive NMDAR antagonist (Stefan et al, 2002;Stefan et al, 2000;Wolters et al, 2003). Furthermore, PAS LTP -induced LTP-like plasticity interacts homeostatically with prior or subsequent motor learning (Elahi et al, 2013;Jung and Ziemann, 2009;Kang et al, 2011;Rosenkranz et al, 2007;Stefan et al, 2006;Ziemann et al, 2004), indicating its mechanistic importance in learning processes.…”