Releasing the Cortical Brake by Non-Invasive Electromagnetic Stimulation? rTMS Induces LTD of GABAergic Neurotransmission

Repetitive Transcranial Magnetic Stimulation (rTMS) is a non-invasive brain stimulation technique which modulates cortical excitability beyond the stimulation period. However, despite its clinical use rTMS-based therapies which prevent or reduce disabilities in a functionally significant and sustained manner are scarce. It remains unclear how rTMS-mediated changes in cortical excitability, which are not task- or input-specific, exert beneficial effects in some healthy subjects and patients. While experimental evidence exists that repetitive magnetic stimulation (rMS) is linked to the induction of long-term potentiation (LTP) of excitatory neurotransmission, less attention has been dedicated to rTMS-induced structural, functional and molecular adaptations at inhibitory synapses. In this review article we provide a concise overview on basic neuroscience research, which reveals an important role of local disinhibitory networks in promoting associative learning and memory. These studies suggest that a reduction in inhibitory neurotransmission facilitates the expression of associative plasticity in cortical networks under physiological conditions. Hence, it is interesting to speculate that rTMS may act by decreasing GABAergic neurotransmission onto cortical principal neurons. Indeed, evidence has been provided that rTMS is capable of modulating inhibitory networks. Consistent with this suggestion recent basic science work discloses that a 10 Hz rTMS protocol reduces GABAergic synaptic strength on principal neurons. These findings support a model in which rTMS-induced long-term depression (LTD) of GABAergic synaptic strength mediates changes in excitation/inhibition-balance of cortical networks, which may in turn facilitate (or restore) the ability of stimulated networks to express input- and task-specific associative synaptic plasticity.