Han Lu, Shreyash Garg, Maximilian Lenz, Andreas Vlachos
{"title":"iTBS600重复性磁刺激诱导小鼠器官型切片培养持续的结构和功能可塑性。","authors":"Han Lu, Shreyash Garg, Maximilian Lenz, Andreas Vlachos","doi":"10.1016/j.brs.2025.07.008","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Repetitive transcranial magnetic stimulation (rTMS) is well known for its ability to induce synaptic plasticity, yet its impact on structural and functional remodeling within stimulated networks remains unclear. This study investigates the cellular and network-level mechanisms of rTMS-induced plasticity using a clinically approved 600-pulse intermittent theta burst stimulation (iTBS600) protocol applied to mouse organotypic brain tissue cultures.</p><p><strong>Methods: </strong>We applied iTBS600 to entorhino-hippocampal organotypic tissue cultures and conducted a 24-hour analysis using c-Fos immunostaining, whole-cell patch-clamp recordings, time-lapse imaging of dendritic spines, and calcium imaging.</p><p><strong>Results: </strong>We observed long-term potentiation (LTP) of excitatory synapses in dentate granule cells, characterized by increased mEPSC frequencies and spine remodeling over time. c-Fos expression in the dentate gyrus was transient and exhibited a clear sensitivity to the orientation of the induced electric field, suggesting a direction-dependent induction of plasticity. Structural remodeling of dendritic spines was temporally linked to enhanced synaptic strength, while spontaneous calcium activity remained stable during the early phase in the dentate gyrus, indicating the engagement of homeostatic mechanisms. Despite the widespread electric field generated by rTMS, its effects were spatially and temporally precise, driving Hebbian plasticity and region-specific spine dynamics.</p><p><strong>Conclusions: </strong>These findings provide mechanistic insights into how rTMS-induced LTP promotes targeted plasticity while preserving network stability. Understanding these interactions may help refine stimulation protocols to optimize therapeutic outcomes.</p>","PeriodicalId":9206,"journal":{"name":"Brain Stimulation","volume":" ","pages":"1392-1402"},"PeriodicalIF":8.4000,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Repetitive magnetic stimulation with iTBS600 induces persistent structural and functional plasticity in mouse organotypic slice cultures.\",\"authors\":\"Han Lu, Shreyash Garg, Maximilian Lenz, Andreas Vlachos\",\"doi\":\"10.1016/j.brs.2025.07.008\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Repetitive transcranial magnetic stimulation (rTMS) is well known for its ability to induce synaptic plasticity, yet its impact on structural and functional remodeling within stimulated networks remains unclear. This study investigates the cellular and network-level mechanisms of rTMS-induced plasticity using a clinically approved 600-pulse intermittent theta burst stimulation (iTBS600) protocol applied to mouse organotypic brain tissue cultures.</p><p><strong>Methods: </strong>We applied iTBS600 to entorhino-hippocampal organotypic tissue cultures and conducted a 24-hour analysis using c-Fos immunostaining, whole-cell patch-clamp recordings, time-lapse imaging of dendritic spines, and calcium imaging.</p><p><strong>Results: </strong>We observed long-term potentiation (LTP) of excitatory synapses in dentate granule cells, characterized by increased mEPSC frequencies and spine remodeling over time. c-Fos expression in the dentate gyrus was transient and exhibited a clear sensitivity to the orientation of the induced electric field, suggesting a direction-dependent induction of plasticity. Structural remodeling of dendritic spines was temporally linked to enhanced synaptic strength, while spontaneous calcium activity remained stable during the early phase in the dentate gyrus, indicating the engagement of homeostatic mechanisms. Despite the widespread electric field generated by rTMS, its effects were spatially and temporally precise, driving Hebbian plasticity and region-specific spine dynamics.</p><p><strong>Conclusions: </strong>These findings provide mechanistic insights into how rTMS-induced LTP promotes targeted plasticity while preserving network stability. 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Repetitive magnetic stimulation with iTBS600 induces persistent structural and functional plasticity in mouse organotypic slice cultures.
Background: Repetitive transcranial magnetic stimulation (rTMS) is well known for its ability to induce synaptic plasticity, yet its impact on structural and functional remodeling within stimulated networks remains unclear. This study investigates the cellular and network-level mechanisms of rTMS-induced plasticity using a clinically approved 600-pulse intermittent theta burst stimulation (iTBS600) protocol applied to mouse organotypic brain tissue cultures.
Methods: We applied iTBS600 to entorhino-hippocampal organotypic tissue cultures and conducted a 24-hour analysis using c-Fos immunostaining, whole-cell patch-clamp recordings, time-lapse imaging of dendritic spines, and calcium imaging.
Results: We observed long-term potentiation (LTP) of excitatory synapses in dentate granule cells, characterized by increased mEPSC frequencies and spine remodeling over time. c-Fos expression in the dentate gyrus was transient and exhibited a clear sensitivity to the orientation of the induced electric field, suggesting a direction-dependent induction of plasticity. Structural remodeling of dendritic spines was temporally linked to enhanced synaptic strength, while spontaneous calcium activity remained stable during the early phase in the dentate gyrus, indicating the engagement of homeostatic mechanisms. Despite the widespread electric field generated by rTMS, its effects were spatially and temporally precise, driving Hebbian plasticity and region-specific spine dynamics.
Conclusions: These findings provide mechanistic insights into how rTMS-induced LTP promotes targeted plasticity while preserving network stability. Understanding these interactions may help refine stimulation protocols to optimize therapeutic outcomes.
期刊介绍:
Brain Stimulation publishes on the entire field of brain stimulation, including noninvasive and invasive techniques and technologies that alter brain function through the use of electrical, magnetic, radiowave, or focally targeted pharmacologic stimulation.
Brain Stimulation aims to be the premier journal for publication of original research in the field of neuromodulation. The journal includes: a) Original articles; b) Short Communications; c) Invited and original reviews; d) Technology and methodological perspectives (reviews of new devices, description of new methods, etc.); and e) Letters to the Editor. Special issues of the journal will be considered based on scientific merit.