Paired associative stimulation induces change in presynaptic inhibition of Ia 1 terminals in wrist flexors in humans

24 Enhancements in the strength of corticospinal projections to muscles are induced in 25 conscious humans by paired associative stimulation (PAS) to the motor cortex. Although 26 most of the previous studies support the hypothesis that the increase of the amplitude of 27 motor evoked potentials (MEP) by PAS involves long-term potentiation (LTP)-like 28 mechanism in cortical synapses, changes in spinal excitability after PAS have been 29 reported, suggestive of parallel modifications in both cortical and spinal excitability. 30 In a first series of experiments (experiment 1), we confirmed that both Flexor Carpi 31 Radialis (FCR) MEPs and FCR H reflex recruitment curves are enhanced by PAS. To 32 elucidate the mechanism responsible for this change in the H reflex amplitude, we tested, 33 using the same subjects, the hypothesis that enhanced H reflexes are due to a down34 regulation of the efficacy of mechanisms controlling Ia afferent discharge, including 35 presynaptic Ia inhibition and post-activation depression. To address this question, 36 amounts of both presynaptic Ia inhibition of FCR Ia terminals (D1and D2 inhibitions 37 methods – experiment 2) and post-activation depression (experiment 3) were determined 38 before and after PAS. Results showed that PAS induces a significant decrease of 39 presynaptic Ia inhibition of FCR terminals, which was concomitant with the facilitation 40 of the H reflex. Post-activation depression was unaffected by PAS. 41 It is argued that enhancement of segmental excitation by PAS relies on a selective effect 42 of PAS on the interneurons controlling presynaptic inhibition of Ia terminals. 43