Abstract
Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive brain stimulation technique that can alter cortical excitability in human subjects for hours beyond the stimulation period. It thus has potential as a therapeutic tool in neuropsychiatric disorders associated with alterations in cortical excitability. However, rTMS-induced neural plasticity remains insufficiently understood at the cellular level. To learn more about the effects of repetitive magnetic stimulation (rMS), we established an in vitro model of rMS using mouse organotypic entorhino-hippocampal slice cultures. We assessed the outcome of a high-frequency (10 Hz) rMS protocol on functional and structural properties of excitatory synapses in mature hippocampal CA1 pyramidal neurons. Whole-cell patch-clamp recordings, immunohistochemistry, and time-lapse imaging techniques revealed that rMS induces a long-lasting increase in glutamatergic synaptic strength, which is accompanied by structural remodeling of dendritic spines. The effects of rMS on spine size were predominantly seen in small spines, suggesting differential effects of rMS on subpopulations of spines. Furthermore, our data indicate that rMS-induced postsynaptic changes depend on the NMDA receptor-mediated accumulation of GluA1-containing AMPA receptors. These results provide first experimental evidence that rMS induces coordinated functional and structural plasticity of excitatory postsynapses, which is consistent with a long-term potentiation of synaptic transmission.
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