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.

译文

重复经颅磁刺激 (rTMS) 是一种非侵入性脑刺激技术,可以在刺激期后数小时内改变人类受试者的皮质兴奋性。因此,它具有作为与皮质兴奋性改变相关的神经精神疾病的治疗工具的潜力。然而,rTMS诱导的神经可塑性在细胞水平上仍未得到充分理解。为了了解有关重复磁刺激 (rMS) 的更多信息,我们使用小鼠器官型entorhino-海马切片培养物建立了rMS的体外模型。我们评估了高频 (10Hz) rMS协议对成熟海马CA1锥体神经元兴奋性突触的功能和结构特性的结果。全细胞膜片钳记录,免疫组织化学和延时成像技术表明,rMS诱导谷氨酸能突触强度的长期增加,并伴随着树突棘的结构重塑。rMS对脊柱大小的影响主要出现在小脊椎中,这表明rMS对脊柱亚群的不同影响。此外,我们的数据表明rMS诱导的突触后变化取决于NMDA受体介导的GluA1-containing AMPA受体的积累。这些结果提供了第一个实验证据,表明rMS诱导兴奋性突触后的协调功能和结构可塑性,这与突触传递的长期增强一致。

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