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-i...
Saved in:
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-09-01
|
| Series: | Brain Stimulation |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1935861X25002761 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850032906600185856 |
|---|---|
| author | Han Lu Shreyash Garg Maximilian Lenz Andreas Vlachos |
| author_facet | Han Lu Shreyash Garg Maximilian Lenz Andreas Vlachos |
| author_sort | Han Lu |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-d95ccd08dbea4414b45a3b65c0c9de1a |
| institution | DOAJ |
| issn | 1935-861X |
| language | English |
| publishDate | 2025-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Brain Stimulation |
| spelling | doaj-art-d95ccd08dbea4414b45a3b65c0c9de1a2025-08-20T02:58:27ZengElsevierBrain Stimulation1935-861X2025-09-011851392140210.1016/j.brs.2025.07.008Repetitive magnetic stimulation with iTBS600 induces persistent structural and functional plasticity in mouse organotypic slice culturesHan Lu0Shreyash Garg1Maximilian Lenz2Andreas Vlachos3Department of Neuroanatomy, Institute of Anatomy and Cell Biology, Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany; BrainLinks-BrainTools Center, University of Freiburg, 79104 Freiburg, Germany; Correspondence to: Institute for Advanced Simulation (IAS), Jülich Supercomputing Center (JSC), Forschungszentrum Jülich, 52428 Jülich, Germany.Department of Neuroanatomy, Institute of Anatomy and Cell Biology, Faculty of Medicine, University of Freiburg, 79104 Freiburg, GermanyDepartment of Neuroanatomy, Institute of Anatomy and Cell Biology, Faculty of Medicine, University of Freiburg, 79104 Freiburg, GermanyDepartment of Neuroanatomy, Institute of Anatomy and Cell Biology, Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany; BrainLinks-BrainTools Center, University of Freiburg, 79104 Freiburg, Germany; Center for Basics in Neuromodulation (NeuroModulBasics), Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany; Correspondence to: Department of Neuroanatomy, Institute of Anatomy and Cell Biology, Faculty of Medicine, University of Freiburg, Albertstrasse 17, 79104 Freiburg, Germany.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.http://www.sciencedirect.com/science/article/pii/S1935861X25002761Magnetic stimulationIntermittent theta-burst stimulation (iTBS)in vitroHebbian plasticityFiring rate homeostasisStructural plasticity |
| spellingShingle | Han Lu Shreyash Garg Maximilian Lenz Andreas Vlachos Repetitive magnetic stimulation with iTBS600 induces persistent structural and functional plasticity in mouse organotypic slice cultures Brain Stimulation Magnetic stimulation Intermittent theta-burst stimulation (iTBS) in vitro Hebbian plasticity Firing rate homeostasis Structural plasticity |
| title | Repetitive magnetic stimulation with iTBS600 induces persistent structural and functional plasticity in mouse organotypic slice cultures |
| title_full | Repetitive magnetic stimulation with iTBS600 induces persistent structural and functional plasticity in mouse organotypic slice cultures |
| title_fullStr | Repetitive magnetic stimulation with iTBS600 induces persistent structural and functional plasticity in mouse organotypic slice cultures |
| title_full_unstemmed | Repetitive magnetic stimulation with iTBS600 induces persistent structural and functional plasticity in mouse organotypic slice cultures |
| title_short | Repetitive magnetic stimulation with iTBS600 induces persistent structural and functional plasticity in mouse organotypic slice cultures |
| title_sort | repetitive magnetic stimulation with itbs600 induces persistent structural and functional plasticity in mouse organotypic slice cultures |
| topic | Magnetic stimulation Intermittent theta-burst stimulation (iTBS) in vitro Hebbian plasticity Firing rate homeostasis Structural plasticity |
| url | http://www.sciencedirect.com/science/article/pii/S1935861X25002761 |
| work_keys_str_mv | AT hanlu repetitivemagneticstimulationwithitbs600inducespersistentstructuralandfunctionalplasticityinmouseorganotypicslicecultures AT shreyashgarg repetitivemagneticstimulationwithitbs600inducespersistentstructuralandfunctionalplasticityinmouseorganotypicslicecultures AT maximilianlenz repetitivemagneticstimulationwithitbs600inducespersistentstructuralandfunctionalplasticityinmouseorganotypicslicecultures AT andreasvlachos repetitivemagneticstimulationwithitbs600inducespersistentstructuralandfunctionalplasticityinmouseorganotypicslicecultures |