Repetitive transcranial magnetic stimulation induces cortical layer, brain region, and protocol dependent neural plasticity [Spatial transcriptomics]

Repetitive transcranial magentic stimulation (rTMS) is a non-invasive toll commonly used to study neural plasticity processes and treat neurological disorders. Despite the popularity of rTMS, it is still unclear what neural plasticity mechanisms are induced in the brain regions at and beyond the stimulation site, and how this varies with different rTMS protocols. Here we used spatial transcriptomics to map the neural plasticity mechanisms induced across cortical and sub-cortical regions following intermittent or continuous theta-burst stimulation protocols to the mouse sensorimotor cortex. Our results revealed that rTMS alters the expression of genes related to several cellular processes and neural plasticity mechanisms across the brain which was both brain region and rTMS protocol dependent. In the cortex, the effect of rTMS was not only dependent on the cortical region, but also the cortical layer within each cortical region. These findings uncover the neural plasticity mechanisms induced across the brain following rTMS and help inform how different stimulation protocols can be used to drive specific neural plasticity mechanisms. Overall design: Wild-type male C57BL/6J mice were treated with a single session of intermittent theta-burst (iTBS), continuous theta-burst (cTBS), or sham stimulation, with four mice used for each stimulatio group. Animals were euthanised three hours post-stimulation and the brains were removed and dissected along the midline. Coronal sections from the right brain hemisphere, taken approximately 0.26 - 0.74 mm anterior from bregma, were analysed using spatial transcriptomics.