Multi-scale modelling of location- and frequency-dependent synaptic plasticity induced by transcranial magnetic stimulation in the dendrites of pyramidal neurons.

Abstract

Repetitive transcranial magnetic stimulation (rTMS) induces long-term changes of synapses, but the mechanisms behind these modifications are not fully understood. Al- though there has been progress in the development of multi-scale modeling tools, no com- prehensive module for simulating rTMS-induced synaptic plasticity in biophysically realistic neurons exists.. We developed a modelling framework that allows the replication and detailed prediction of long-term changes of excitatory synapses in neurons stimulated by rTMS. We implemented a voltage-dependent plasticity model that has been previously established for simulating frequency-, time-, and compartment-dependent spatio-temporal changes of excitatory synapses in neuronal dendrites. The plasticity model can be incorporated into biophysical neuronal models and coupled to electrical field simulations. We show that the plasticity modelling framework replicates long-term potentiation (LTP)-like plasticity in hippocampal CA1 pyramidal cells evoked by 10-Hz repetitive magnetic stimulation (rMS). This plasticity was strongly distance dependent and concentrated at the proximal synapses of the neuron. We predicted a decrease in the plasticity amplitude for 5 Hz and 1 Hz protocols with decreasing frequency. Finally, we successfully modelled plasticity in distal synapses upon local electrical theta-burst stimulation (TBS) and predicted proximal and distal plasticity for rMS TBS. Notably, the rMS TBS-evoked synaptic plasticity exhibited robust facilitation by dendritic spikes and low sensitivity to inhibitory suppression. The plasticity modelling framework enables precise simulations of LTP-like cellular effects with high spatio-temporal resolution, enhancing the efficiency of parameter screening and the development of plasticity-inducing rTMS protocols. First rigorously validated model of TMS-induced long-term synaptic plasticity in ex- tended neuronal dendrites that goes beyond point-neuron and mean-field modellingRobust simulations of experimental data on LTP-like plasticity in the proximal dendrites of CA1 hippocampal pyramidal cells evoked by 10 Hz repetitive magnetic stimulation (rMS)Replication of distal synaptic plasticity for a local electrical theta burst stimulation (TBS) protocolPrediction of distal and proximal LTP-like plasticity for rMS TBS1 Hz rMS does not induce long-term depression.