Subthreshold repetitive transcranial magnetic stimulation drives structural synaptic plasticity in the young and aged motor cortex

Abstract

Background: Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive tool commonly used to drive neural plasticity in the young adult and aged brain. Recent data from mouse models have shown that even at subthreshold intensities (0.12 T), rTMS can drive neuronal and glial plasticity in the motor cortex. However, the physiological mechanisms underlying subthreshold rTMS induced plasticity and whether these are altered with normal ageing are unclear. Objective: To assess the effect of subthreshold rTMS, using the intermittent theta burst stimulation (iTBS) protocol on structural synaptic plasticity in the mouse motor cortex of young and aged mice. Methods: Longitudinal in vivo 2-photon microscopy was used to measure changes to the structural plasticity of pyramidal neuron dendritic spines in the motor cortex following a single train of subthreshold rTMS (in young adult and aged animals) or the same rTMS train administered on 4 consecutive days (in young adult animals only). Data were analysed with Bayesian hierarchical generalized linear regression models and interpreted with the aid of Bayes Factors (BF). Results: We found strong evidence (BF > 10) that subthreshold rTMS altered the rate of dendritic spine losses and gains, dependent on the number of stimulation sessions and that a single session of subthreshold rTMS was effective in driving structural synaptic plasticity in both young adult and aged mice. Conclusion: These findings provide further evidence that rTMS drives synaptic plasticity in the brain and uncovers structural synaptic plasticity as a key mechanism of subthreshold rTMS induced plasticity.

Effectiveness of cerebellar vermis intermittent theta-burst stimulation in improving trunk control and balance function for patients with subacute stroke: a randomised controlled trial protocol

“…Studies with humans have shown that iTBS drives acute changes to motor behaviour and neuronal excitability. 60 A possible mechanism has been reported by an animal study showing that iTBS can promote neural structural remodelling and functional recovery by enhancing neurogenesis and migration via the miR-551b-5p/BDNF/TrkB pathway. 61 The first study of cerebellar vermis stimulation was reported in 1995, which investigated its effects on saccade metrics in a man via TMS.…”

Manipulating the Level of Sensorimotor Stimulation during LI-rTMS Can Improve Visual Circuit Reorganisation in Adult Ephrin-A2A5-/- Mice

“…The rTMS-induced changes to cortical physiology have been suggested to resemble those occurring during the critical or sensitive period of development [ 46 ] and may increase the capacity for plasticity in the mature brain [ 47 , 48 , 49 ]. For example, rTMS has been shown to increase the expression of brain-derived neurotrophic factor (BDNF) [ 21 , 22 , 50 , 51 , 52 ], disinhibit cortical circuits [ 53 , 54 , 55 , 56 ], and alter dendritic spine density in motor cortex [ 57 ]. Thus, the outcomes of rTMS-based therapies may modify and facilitate the removal of barriers to adult plasticity to create a more adaptive environment, in which endogenous brain activity can drive relevant and beneficial functional changes.…”

Microglia associations with brain pericytes and the vasculature are reduced in Alzheimer’s disease

“…Cranial windows were implanted in nine 12-week-old NG2DsRed x CX3CR1 +/GFP mice as described previously 60 , with modification; windows were implanted without a titanium bar glued opposite the window and were placed over the primary somatosensory cortex, specifically over the upper, lower and trunk domain areas. In vivo two-photon laser scanning microscopy (2PLSM) was performed using the same microscope and software as previously described 60 and was performed during the mouse light cycle. To image blood vessels, mice were intravenously (via the tail vein) administered 2% w/v FITC-dextran in saline (70,000 Da; Sigma-Aldrich, USA) 10 minutes prior to imaging.…”

“…To image blood vessels, mice were intravenously (via the tail vein) administered 2% w/v FITC-dextran in saline (70,000 Da; Sigma-Aldrich, USA) 10 minutes prior to imaging. Mice were anesthetised with isoflurane in a chamber, then transferred to a stereotaxic frame, where isoflurane was delivered through a facemask at 2-3% concentration in oxygen, as required, to maintain anaesthesia 60 . An EC Plan-Neofluar 20X/0.1 water immersion objective (Nikon, USA), illuminated by white light, was used to identify large blood vessels in the somatosensory cortex (layers II/III) that were subsequently used as landmarks for regions of interest (ROIs).…”