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

Abstract

Transcranial magnetic stimulation (TMS) is a widely used non-invasive technique in research and clinical settings. Despite its success, the cellular and molecular mechanisms underlying TMS-induced changes in the brain remain incompletely understood. Current protocols are largely heuristic, based on system-level observations. This study employed in vitro repetitive magnetic stimulation (rMS) in mouse brain tissue cultures, combined with computational modeling to develop an experimentally validated approach for predicting TMS effects. Unlike electrical or optogenetic stimulation, rTMS uniquely enhances plasticity by activating both pre- and postsynaptic neurons, with brain-derived neurotrophic factor (BDNF) playing a crucial role. Our simulations accurately predicted the frequency-dependent effects of rTMS, providing a critical step towards developing robust, validated tools that will enhance the precision and effectiveness of TMS applications across both research and clinical settings. Significance StatementThis study elucidates the mechanisms by which TMS promotes neural plasticity, specifically long-term potentiation (LTP) of excitatory neurotransmission. By demonstrating that rMS engages both pre- and postsynaptic neurons with BDNF as a key mediator, it provides a mechanistic basis for the therapeutic effects of rTMS. These insights advance our understanding of rTMS-induced brain plasticity and support the development of predictive computer models, paving the way for more effective and standardized TMS protocols in research and clinical applications.