Transcranial magnetic stimulation has been shown to produce benefits in some studies, but reproduction in this field is challenging. There are many options for equipment, frequency, power, duration of treatment, and so forth, and many of these parameters are (a) likely important in determining whether or not the treatment has any beneficial effect and (b) incompletely specified in publications. Further, the mechanisms by which transcranial magnetic stimulation produces benefits are far from completely understood, making it much harder to calibrate potential therapies than would otherwise be the case. Here find an example of research in this part of the field, in which scientists explore the effects of transcranial magnetic stimulation on some of the smaller structures in neurons and neural connections.
Axonal boutons are specialized endings of an axon, which is the long slender part of a neuron that connects neurons by transmitting neural signals. These are sites where synapses form, allowing neurons to communicate. Therefore, any change in the number or function of these boutons can have profound effects on brain connectivity. In this study, the researchers observed structural changes of two types of excitatory boutons, namely “terminaux boutons” (TBs) (short protrusions from the axon shaft typically connecting neurons in a local area) and “en passant boutons” (EPBs) (small bead-like structures along axons typically connecting distal regions). They used two-photon imaging to visualize individual axons and synapses in the brain of a live animal.
The study was conducted on the APP/PS1 x Thy-1GFP-M strain of mice, which is a cross between the APP/PS1 strain (genetically modified to show Alzheimer’s disease (AD)-like symptoms seen in humans) and the Thy1-GFP-M strain, which expresses a fluorescent protein in certain neurons. This combination causes axons to glow during imaging, enabling precise tracking of synaptic bouton changes over time. The team monitored the dynamics of the axonal boutons in these mice at 48-hour intervals for eight days, both before and after a single repetitive transcranial magnetic stimulation (rTMS) session. They then compared these findings to healthy wild-type (WT) mice.
They found that both TBs and EPBs in the AD mouse model had comparable density to those in healthy WT mice. However, the turnover of both bouton types was significantly lower in the AD mouse model before rTMS, likely due to the amyloid plaque buildup, a key marker of dementia, and potentially causing diseases like AD. After a single session of low-intensity rTMS, the turnover of TBs in both strains increased significantly, while there was no change in the EPB turnover. Furthermore, in the AD mouse model, this increased turnover was comparable to the turnover levels in the WT mice seen before stimulation. This indicates that low-intensity rTMS can potentially restore the synaptic plasticity of TBs to those seen in healthy mice. Moreover, the fact that only TBs, and not EPBs, responded to rTMS points to the possibility that the mechanisms of rTMS might be cell-type specific.
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