Microglial cytokines mediate plasticity induced by 10 Hz repetitive magnetic stimulation

Microglia—the resident immune cells of the central nervous system—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 employed non-invasive brain stimulation technique, on microglia-mediated synaptic plasticity. 10 Hz electromagnetic stimulation triggered a release of plasticity-promoting cytokines from microglia in organotypic brain tissue cultures, while no changes in microglial morphology or microglia dynamics were observed. Indeed, substitution of tumor necrosis factor alpha (TNFα) and interleukin 6 (IL6) preserved synaptic plasticity induced by 10 Hz stimulation in the absence of microg..., Ethics statement. Mice were maintained in a 12 h light/dark cycle with food and water available ad libitum. Every effort was made to minimize distress and pain of animals. All experimental procedures were performed according to German animal welfare legislation and approved by the competent authority (Regierungspräsidium Freiburg, G-20/154) appropriate animal welfare committee and the animal welfare officer of Albert-Ludwigs-University Freiburg, Faculty of Medicine (X-17/07K, X-17/09C, X-18/02C).
Preparation of tissue cultures. Entorhino-hippocampal tissue cultures were prepared at postnatal day 3–5 from C57BL/6J, HexB-tdTom (Masuda et al., 2020), and C57BL/6-Tg(TNFa-eGFP) (Lenz et al., 2020) mice of either sex as previously described (Del Turco and Deller, 2007). Cultivation medium contained 50% (v/v) MEM, 25% (v/v) basal medium eagle, 25% (v/v) heat-inactivated normal horse serum, 25 mM HEPES buffer solution, 0.15% (w/v) bicarbonate, 0.65% (w/v) glucose, 0.1 mg/ml streptomycin, 100 U/..., Data were analyzed using GraphPad Prism 7 and 9 (GraphPad software, USA).