Repetitive magnetic stimulation induces plasticity of excitatory synapses through cooperative pre- and postsynaptic activity
Christos Galanis, Nicholas Hananeia, Maximilian Lenz, Mohammadreza Vasheghani Farahani, Peter Jedlička, Andreas Vlachos
Abstract
INTRODUCTION: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.