Paired Associative Stimulation Fails to Induce Plasticity in Freely Behaving Intact Rats

Abstract

Paired Associative Stimulation (PAS) has been explored in humans as a non-invasive tool to drive plasticity and promote recovery after neurological insult. A more thorough understanding of the phenomenon of PAS-induced plasticity is needed to fully harness it as a clinical tool. Here, we tested a PAS model in awake rats in order to study the principles of associative plasticity. Using chronically implanted electrodes in motor cortex and forelimb, we explored PAS parameters to effectively change corticomotor excitability, assessed using closed loop, EMG-controlled cortical stimulation. We tested eleven stimulation intervals, chosen to force the coincidence of neuronal activity in the rats motor cortex and spinal cord, 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.