Spinal associative plasticity in depth: evidence from animal model

Spike-timing dependent plasticity (STDP) implies changes in the effectiveness of the synapse strength depending on exact timing of pre- and postsynaptic activation. STDP is thought to mediate forms of associative plasticity based on the Hebbian theory. Associative plasticity can be probed experimentally and non-invasively in humans by applying “paired associative stimulation” (PAS). The original PAS protocol described in humans (Stefan et al. 2000) consists of repetitive cortical and peripheral nerve stimuli delivered at specific interstimulus intervals (ISIs), able to elicit long-term potentiation (LTP)- and depression (LTD)- like plasticity in the primary motor cortex (M1). More recently, a number of modified PAS protocols have been designed and tested in humans such as protocols able to promote plasticity in the spinal cord (Suppa et al. 2017). Spinal PAS might be in theory applied to harness plasticity for motor recovery in patients with various neurological disorders. However, a number of issues, including the specific physiological basis of plasticity induced by various spinal PAS protocols, remain to be clarified. Understanding the precise neurophysiological basis of spinal associative plasticity is the necessary precondition of development of new non-invasive neurostimulation strategies in human neurological disorders.