Interaction of LTP-Like and LTD-Like Plasticity and Motor Learning in Healthy Human Subjects

Abstract

Motor learning is essential for the acquisition and rehabilitation of motor skills. It is supposed that rapid learning occurs through modification of synaptic strength in which long-term potentiation (LTP) and long-term depression (LTD) form the most important mechanisms. The Bienenstock-Cooper-Munro (BCM) theory states that the threshold for LTP induction increases and for LTD induction decreases if LTP was involved in a preceding learning process. The aim of the present experiments was to verify this prediction of the BCM theory in humans. For motor practice (MP), subjects were instructed to perform 450 fastest possible thumb movements at a rate of 0.5Hz; the subsequent increase in maximum peak acceleration of the practiced movement was defined as motor learning. Moreover, we induced LTP-like and LTD-like plasticity in the intact human primary motor cortex (M1) by an established paired associative stimulation (PAS) protocol. PAS consisted of 200–225 pairs of electrical stimulation of the right median nerve, followed by focal transcranial magnetic stimulation (TMS) of the hand area of the left M1. The interstimulus interval equalled the individual N20 latency of the median nerve somatosensory-evoked cortical potential (PASN20) or was 5 ms less (PASN20–5). PASN20 induced reproducibly an LTP-like long-lasting (>30min) increase in the amplitude of motor-evoked potentials (MEP) in the prime mover muscle of MP, whereas PASN20–5 induced an LTD-like decrease. As a control condition, a 100 ms interstimulus interval was used in the PAS protocol (PAS100), which had no significant effect on MEP amplitude. Experiment 1 (MP preceding PAS): If MP preceded PASN20, the LTP-like MEP increase produced by PASN20 alone was abolished, even with a trend toward a depression of MEP amplitude. In contrast, if MP preceded PASN20–5, the LTD-like MEP decrease produced by PASN20–5 alone was enhanced. Experiment 2 (PAS preceding MP): PASN20–5 prior to MP resulted in a better learning performance (larger increase in maximum peak acceleration) than PAS100 prior to MP. In contrast, motor learning subsequent to PASN20 did not differ from motor learning following PAS100. These findings support the view that learning in human cortex occurs through LTP-like mechanisms. Moreover, our data maintain the prediction derived from the BCM theory that previous induction of LTD-like plasticity enhances LTP-dependent motor learning.