Microcircuit mechanisms involved in paired associative stimulation‐induced depression of corticospinal excitability

• Published in: The Journal of physiology 2013-10, Vol.591 (19), p.4903-4920
• Main Authors: Weise, David, Mann, Jakob, Ridding, Michael, Eskandar, Kevin, Huss, Martin, Rumpf, Jost‐Julian, Di Lazzaro, Vincenzo, Mazzone, Paolo, Ranieri, Federico, Classen, Joseph
• Format: Article
• Language: English
• Subjects: Action Potentials; Adult; Cerebral Cortex - physiology; Evoked Potentials, Motor; Evoked Potentials, Somatosensory; Female; Humans; Interneurons - physiology; Male; Muscle, Skeletal - innervation; Muscle, Skeletal - physiology; Neural Inhibition; Neuronal Plasticity; Neurons; Neuroscience: Development/Plasticity/Repair; Pyramidal Tracts - physiology; Pyramidal Tracts - physiopathology; Spinal Cord Injuries - physiopathology; Synapses - physiology; Transcranial Magnetic Stimulation
• ISSN: 0022-3751; 1469-7793
• DOI: 10.1113/jphysiol.2013.253989

Key points •  Repetitively pairing peripheral nerve stimulation with transcranial magnetic stimulation of the corresponding contralateral motor cortex at 10 ms (paired associative stimulation; PAS10) leads to centre‐depressant effects on corticospinal excitability in a short time window. •  PAS10‐induced centre‐depressant effects are due to weakening of excitatory synapses between principal cortical neurons, but not those located on corticospinal neurons, or inhibitory synapses. •  Inhibitory interneurons are gate‐keepers to producing centre‐depressant PAS effects. The same mechanisms appear to govern PAS10‐induced surround‐facilitatory effects. •  We propose a model specifying the composition and laminar location of the involved microcircuit of PAS‐induced plasticity that may enhance its utility as a model of spike‐timing‐ dependent plasticity in humans.   Synaptic weight changes induced by temporal correlations between the spikes of pre‐ and postsynaptic neurons are referred to as spike‐timing‐dependent plasticity (STDP). Transcranial magnetic stimulation (TMS) induces long‐lasting effects on corticospinal excitability, if it is repetitively paired with stimulation of afferents from a corresponding contralateral hand region at short intervals (paired associative stimulation, PAS). PAS‐induced plasticity has been linked with synaptic STDP. We aimed to investigate which elements of the cortical microcircuitry sustain and govern PAS‐induced depression of corticospinal excitability in the target muscle representation (and enhancement of excitability in its functional surround). We show that the time window during which the interaction between both stimulus‐induced cortical events leads to immediate post‐interventional depression is short (