Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation technique that uses magnetic waves to stimulate neuronal elements. Administering low intensity (LI)-rTMS immediately before learning has been shown to enhance reaching accuracy in a rodent skilled reaching task (Tang et al., 2018). While the effects of rTMS can be long-lasting, the mechanism underlying these effects remains unclear.

Our study investigates how delivering LI-rTMS prior to a skilled reaching task affects structural synaptic plasticity in the mouse motor cortex. We employed longitudinal in vivo 2-photon microscopy to observe changes in dendritic spines of pyramidal neurons in Thy1-gfp-M mice. Mice were divided into two groups and received LI-rTMS (n=4) or sham LI-rTMS (n=5) immediately before a 10-day skilled reaching task. Daily imaging was performed through a cranial window after the task, with spines recorded as stable, new, or lost.

All mice improved in performance over the 10-day period. In the learning only (sham LI-rTMS) group, we observed a decrease in synaptic gains during the first three days of the task, with no changes in spine losses, stability, survival, or density. In contrast, mice that received LI-rTMS showed destabilization of newly formed dendritic spines, leading to lower spine survival rates compared to spines formed before the task. Additionally, LI-rTMS caused a small but significant increase in spine gains on day three, raising spine density. These alterations were transient returning to baseline following task cessation.

These findings suggest that LI-rTMS, when used as a primer for a learning task, can modulate synaptic plasticity.