Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive method used clinically to modulate brain activity. While it is known to influence synaptic function, it has remained unclear how stimulation reshapes neuronal circuits at both functional and structural levels in a coordinated manner.
In a study published in Brain Stimulation, Dr. Han Lu and colleagues investigated the effects of a clinically approved intermittent theta-burst stimulation protocol (iTBS600) using mouse entorhino-hippocampal slice cultures — a well-established model to study synaptic plasticity in defined neural networks.
The key findings were:
- Long-term potentiation (LTP) was induced at excitatory synapses of dentate granule cells.
- This functional strengthening was accompanied by persistent structural remodeling of dendritic spines, the small protrusions that host excitatory synapses.
- Structural and functional changes occurred in a temporally coordinated manner, indicating tightly linked plasticity mechanisms.
- Although the induced electric field was spatially widespread, plasticity expression was highly specific, with transient orientation-dependent activation patterns revealed by c-Fos expression.
- Importantly, early spontaneous calcium network activity in the dentate gyrus remained stable after stimulation, suggesting engagement of homeostatic mechanisms that maintain overall network balance.
These results demonstrate that rTMS can promote targeted Hebbian plasticity while preserving global network stability. The study provides mechanistic insight into how clinically relevant stimulation protocols reshape neuronal circuits and may help refine therapeutic applications of non-invasive brain stimulation.
Lu H, Garg S, Lenz M, Vlachos A (2025) Repetitive magnetic stimulation with iTBS600 induces persistent structural and functional plasticity in mouse organotypic slice cultures. Brain Stimul 18(5):1392-1402. doi: 10.1016/j.brs.2025.07.008.
