Pulse number determines synaptic plasticity threshold during intermittent theta-burst magnetic stimulation

Abstract

Repetitive transcranial magnetic stimulation (rTMS) is widely used to modulate cortical excitability in clinical and experimental settings. Previous work has established that 10 Hz repetitive magnetic stimulation (rMS) reliably induces excitatory synaptic plasticity in mouse entorhino-hippocampal tissue cultures. Here, we examined whether intermittent theta-burst stimulation with 600 pulses (iTBS600), a clinically established protocol, induces comparable plasticity in this preclinical model. Under our experimental conditions, iTBS600 failed to induce measurable changes at excitatory and inhibitory synapses in CA1 pyramidal neurons. In contrast, increasing the total number of pulses to 900, while preserving the temporal structure of iTBS (iTBS900), robustly potentiated excitatory synaptic strength while reducing inhibitory synaptic strength. These findings identify total pulse number as an important determinant of rMS-induced excitatory and inhibitory synaptic plasticity, consistent with the presence of an effective stimulation threshold under constant stimulation conditions. They further suggest that stimulation dose—defined here as total pulse number at fixed electric field strength and temporal pattern—is an important parameter governing plasticity induction and should be carefully considered in the design and interpretation of patterned rTMS protocols.