Summary: New research demonstrates that low-intensity repetitive transcranial magnetic stimulation (rTMS) can restore important synaptic structures in a mouse model of Alzheimer’s disease (AD). The study reveals that axonal boutons—specialized presynaptic endings where neurons connect—show reduced turnover in AD mice, reflecting impaired synaptic plasticity. A single low-intensity rTMS session selectively increased turnover of one bouton type, bringing it closer to levels observed in healthy animals.
These results suggest rTMS can partially reverse synaptic deficits associated with amyloid pathology, indicating a possible route to improve cortical connectivity and cognitive resilience in AD.
Key Facts:
- Synaptic turnover enhancement: rTMS increased turnover of terminaux boutons (TBs) by up to 213% in the AD mouse model.
- Cell-type specificity: Only terminaux boutons responded to rTMS; en passant boutons (EPBs) did not show a comparable change.
- Therapeutic potential: Low-intensity rTMS restored impaired TB plasticity toward levels seen in healthy wild-type mice.
Source: SPIE
Background: Alzheimer’s disease is a progressive neurodegenerative disorder that undermines memory and cognition in millions of older adults worldwide. One of the earliest and most consequential changes in AD is synaptic dysfunction: the loss of the brain’s ability to add, remove, or reorganize synaptic contacts that encode learning and memory.
Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive brain stimulation technique that delivers electromagnetic pulses to targeted cortical areas. Prior studies indicate that rTMS can enhance synaptic plasticity in healthy brains and has therapeutic applications in several neuropsychiatric and neurodegenerative conditions. However, responses to rTMS in AD are variable and the cellular mechanisms that mediate any benefit are not fully defined.
To investigate how rTMS acts on synapses affected by amyloid pathology, researchers from the University of Queensland and the Wicking Dementia Research and Education Centre at the University of Tasmania examined axonal bouton dynamics in an APP/PS1 amyloidosis mouse model crossed with Thy1-GFP-M fluorescent reporters. Their findings are published in Neurophotonics.
Axonal boutons are presynaptic specializations where synapses form. The study focused on two excitatory bouton subtypes: terminaux boutons (TBs), short protrusions from the axon shaft that typically mediate local connections, and en passant boutons (EPBs), bead-like swellings along axons that commonly form more distal contacts. Using in vivo two-photon microscopy, the team visualized fluorescently labeled cortical axons and monitored individual boutons at 48-hour intervals across an eight-day period surrounding a single rTMS session.
The mouse model combined APP/PS1 genetic amyloid pathology with Thy1-GFP-M labeling, enabling precise longitudinal tracking of bouton presence, formation, and elimination. The investigators compared bouton density and turnover in APP/PS1 x Thy1-GFP-M mice with wild-type (WT) controls, both before and after low-intensity rTMS.
Before stimulation, overall bouton density was similar between AD-model and WT mice, but bouton dynamics—the fraction of boutons gained or lost over time—were significantly reduced in the APP/PS1 mice. This reduction in turnover reflects diminished synaptic plasticity, consistent with amyloid-associated synaptic dysfunction.
Following a single low-intensity rTMS session, terminaux bouton dynamics increased robustly in both WT and APP/PS1 mice, while en passant boutons showed no significant change. The largest effect occurred two days after stimulation: TB turnover rose by about 88% in WT mice and by approximately 213% in APP/PS1 mice. By day eight the increased turnover subsided toward baseline levels. Importantly, TB turnover in stimulated APP/PS1 mice reached values comparable to pre-stimulation WT levels, indicating partial restoration of synaptic flexibility.
The selective responsiveness of TBs suggests that rTMS may act through mechanisms that differ across presynaptic cell types or synaptic architectures. These findings provide the first direct in vivo evidence that presynaptic boutons in both healthy and amyloid-affected cortical circuits can respond to rTMS with increased structural plasticity.
While further work is needed to link these structural changes to behavioral outcomes and to optimize stimulation protocols, the study supports rTMS as a promising, targeted strategy to rescue synaptic deficits in AD and complements previous reports of functional improvement following stimulation.
About this brain stimulation and Alzheimer’s disease research news
Author: Daneet Steffens
Source: SPIE
Contact: Daneet Steffens – SPIE
Image: The image is credited to Neuroscience News
Original Research: Open access.
“Repetitive transcranial magnetic stimulation increases synaptic plasticity of cortical axons in the APP/PS1 amyloidosis mouse model” by Barbora Fulopova et al., Neurophotonics
Abstract
Repetitive transcranial magnetic stimulation increases synaptic plasticity of cortical axons in the APP/PS1 amyloidosis mouse model
Significance
Growing evidence highlights the therapeutic potential of rTMS for dementias, including Alzheimer’s disease. However, individual responses vary and the neural mechanisms remain incompletely understood.
Aim
Because synaptic dysfunction is central to cognitive decline in dementia, the study examined how rTMS affects cortical synapses in an APP/PS1 amyloidosis mouse model crossed with Thy1-driven fluorescent reporters.
Approach
Using in vivo two-photon imaging, the researchers quantified plasticity of excitatory terminaux (TB) and en passant (EPB) axonal boutons at 48-hour intervals for eight days before and after a single session of rTMS.
Results
Both bouton types maintained similar overall numbers pre- and post-stimulation in WT and APP/PS1 groups. However, APP/PS1 axons showed significantly reduced dynamic fractions pre-stimulation. After rTMS, TB dynamics increased in both groups while EPB dynamics did not change.
Conclusions
These findings point to cell type–specific mechanisms of rTMS action and, together with prior reports of functional benefit, support further exploration of rTMS as a potential clinical approach to manage synaptic deficits in Alzheimer’s disease.