RT Journal Article SR Electronic T1 Paired Associative Stimulation Fails to Induce Plasticity in Freely Behaving Intact Rats JF eneuro JO eNeuro FD Society for Neuroscience SP ENEURO.0396-19.2020 DO 10.1523/ENEURO.0396-19.2020 VO 7 IS 2 A1 Windsor Kwan-Chun Ting A1 Maxime Huot-Lavoie A1 Christian Ethier YR 2020 UL http://www.eneuro.org/content/7/2/ENEURO.0396-19.2020.abstract AB Paired associative stimulation (PAS) has been explored in humans as a noninvasive tool to drive plasticity and promote recovery after neurologic insult. A more thorough understanding of PAS-induced plasticity is needed to fully harness it as a clinical tool. Here, we tested the efficacy of PAS with multiple interstimulus intervals in an awake rat model to study the principles of associative plasticity. Using chronically implanted electrodes in motor cortex and forelimb, we explored PAS parameters to effectively drive plasticity. We assessed changes in corticomotor excitability using a closed-loop, EMG-controlled cortical stimulation paradigm. We tested 11 PAS intervals, chosen to force the coincidence of neuronal activity in the motor cortex and spinal cord of rats with timings relevant to the principles of Hebbian spike timing-dependent plasticity. However, despite a relatively large number of stimulus pairings (300), none of the tested intervals reliably changed corticospinal excitability relative to control conditions. Our results question PAS effectiveness under these conditions.