144. Evidence of heterosynaptic interactions in human associative plasticity

Abstract

Paired associative stimulation (PAS) is a method to study motor cortex synaptic plasticity. If a repetitive electrical stimulus to the median nerve is paired with a transcranial magnetic stimulus (TMS) pulse over the controlateral motor cortex at an interstimulus interval (ISI) of 21.5–25 ms, a long term potentiation (LTP)-like synaptic plasticity is induced in the corticospinal system. We investigated the synaptic spatial specificity of PAS25 and PAS21.5, considered to have similar synaptic mechanisms until recently. Eight subjects (28.6 ± 8.3 years) were selected from a sample of 20 subjects because they showed the expected facilitation after both standard PAS protocols and participated to two sessions in which PAS consisted of 360 electrical stimuli (varPAS) paired with TMS over the hotspot of APB. ISI25 ms (varPAS25) and 21.5 ms (varPAS21.5) were randomly delivered for a total of 360 stimuli. Since cerebellar transcranial direct stimulation (TDCS) can abolish the effects of PAS25, either sham or anodal TDCS (2 mA,30 min) was applied to the cerebellum simultaneously with PAS (anodal-varPAS and sham-varPAS). We measured MEPs before and after each intervention. Randomly delivered PAS25 and PAS21.5 (sham-varPAS) blocked the induction of PAS plasticity while the concurrent anodal TDCS (anodal-varPAS) restored the expected effect. PAS25 and PAS21.5 are inducing LTP-like synaptic plasticity with different synaptic spatial specificity. Heterosynaptic LTD-like modulation might well explain the loss of effect of combining PAS21.5 and PAS25.