Microglial Cytokines Mediate Plasticity Induced by 10 Hz Repetitive Magnetic Stimulation

Microglia, the resident immune cells of the CNS, sense the activity of neurons and regulate physiological brain functions. They have been implicated in the pathology of brain diseases associated with alterations in neural excitability and plasticity. However, experimental and therapeutic approaches that modulate microglia function in a brain region-specific manner have not been established. In this study, we tested for the effects of repetitive transcranial magnetic stimulation (rTMS), a clinically used noninvasive brain stimulation technique, on microglia-mediated synaptic plasticity; 10 Hz electromagnetic stimulation triggered a release of plasticity-promoting cytokines from microglia in mouse organotypic brain tissue cultures of both sexes, while no significant changes in microglial morphology or microglia dynamics were observed. Indeed, substitution of tumor necrosis factor a (TNFa) and interleukin 6 (IL6) preserved synaptic plasticity induced by 10 Hz stimulation in the absence of microglia. Consistent with these findings, in vivo depletion of microglia abolished rTMS-induced changes in neurotransmission in the mPFC of anesthetized mice of both sexes. We conclude that rTMS affects neural excitabil-ity and plasticity by modulating the release of cytokines from microglia.

Automated summary

This study demonstrates that repetitive transcranial magnetic stimulation (rTMS) can modulate the release of cytokines from microglia, thereby affecting neural excitability and plasticity, and altering neurotransmission and synaptic plasticity. This finding provides a new approach for the treatment of brain diseases associated with alterations in neural plasticity.