Repetitive magnetic stimulation induces plasticity of excitatory synapses through cooperative pre- and postsynaptic...

Transcranial magnetic stimulation (TMS) is a widely used non-invasive technique, yet its cellular and molecular mechanisms remain incompletely understood. Current protocols are largely heuristic, based on system-level observations. This study explores how 10 Hz repetitive magnetic stimulation (rMS) induces synaptic plasticity by integrating in vitro models with computational simulations.

Mouse organotypic brain tissue cultures were exposed to 10 Hz rMS (900 pulses). Electrophysiology, optogenetic and chemogenetic tools assessed synaptic plasticity mechanisms. Computational modeling based on spike-timing-dependent plasticity (STDP) predicted stimulation outcomes, and pharmacological interventions tested the role of brain-derived neurotrophic factor (BDNF)/tropomyosin receptor kinase B (TrkB) signaling.

Unlike electrical or optogenetic stimulation, 10 Hz rMS enhanced excitatory neurotransmission via coordinated pre- and postsynaptic activation, with BDNF playing a crucial role. Computational modeling accurately predicted frequency-dependent effects. Blocking BDNF/TrkB signaling prevented rMS-induced potentiation, while TrkB activation converted electrically induced LTD into LTP.

These findings support a mechanistic contribution of STDP and BDNF/TrkB signaling to rMS-induced synaptic changes, providing a foundation for future experimental, computational and potentially clinical investigations.