Repetitive transcranial magnetic stimulation (rTMS) is used as a therapeutic tool in neurology and psychiatry. While repetitive magnetic stimulation (rMS) has been shown to induce plasticity of excitatory synapses, it is unclear whether rMS can also modify structural and functional properties of inhibitory inputs. Here we employed 10-Hz rMS of entorhinohippocampal slice cultures to study plasticity of inhibitory neurotransmission on CA1 pyramidal neurons. Our experiments reveal a rMS-induced reduction in GABAergic synaptic strength (2-4 h after stimulation), which is Ca2+-dependent and accompanied by the remodelling of postsynaptic gephyrin scaffolds. Furthermore, we present evidence that 10-Hz rMS predominantly acts on dendritic, but not somatic inhibition. Consistent with this finding, a reduction in clustered gephyrin is detected in CA1 stratum radiatum of rTMS-treated anaesthetized mice. These results disclose that rTMS induces coordinated Ca2+-dependent structural and functional changes of specific inhibitory postsynapses on principal neurons.
Bibliographical noteFunding Information:
We thank Charlotte Nolte-Uhl and Nadine Zahn for their skillful assistance in tissue culturing, and Drs Heinrich Betz and Theofilos Papadopoulos for helpful discussions. This work was supported by Paul and Ursula Klein-Foundation, Dr Paul and Cilli Weill-Foundation (both to A.V.), by Deutsche Forschungsgemeinschaft (FOR1332, CRC1080 to T.D. and A.V.) and by the Federal Ministry of Education and Research, Germany (BMBF; GCBS-WP1 to K.F. and A.V.).