Figure 1.

Repetitive magnetic stimulation (rMS) induces long-term depression (LTD) of inhibitory postsynapses on principal neurons. (A_1–3) Local disinhibitory networks have been recently implicated in gating the ability of principal neurons to express associative excitatory synaptic plasticity. Schematic representation of mechanisms mediating disinhibition of principal neurons (gamma-aminobutyric acid, GABA; acetylcholine, ACh; arrows indicate direction of changes in neurotransmission). (B) Picture depicting a figure-of-eight magnetic stimulation coil (70 mm outer wing diameter). (C) Recent basic science work discloses that 10 Hz rMS induces Ca²⁺-dependent LTD of inhibitory postsynapses on principal neurons. These changes depend on the remodeling of gephyrin, the major postsynaptic scaffolding protein to which GABA_A-receptors anchor. (C_1,2) show examples of original data illustrating changes in gephyrin and GABA_A-receptor subunit α2 clusters 3 h after 10 Hz rMS of organotypic slice cultures (CA1 stratum radiatum, rad; scale bars: 4 μm; see, Lenz et al., 2016). (D) Activation of voltage-gated sodium channels (VGSC), L-type voltage-gated calcium channels (L-VGCC), N-methyl-D-aspartate receptors (NMDAR), and calcineurin protein phosphatase is required during stimulation for rMS-induced LTD of inhibition to occur. It is conceivable that rTMS-induced local disinhibition may facilitate the ability of stimulated neurons to express task-/input-specific associative excitatory synaptic plasticity.