Intermittent Theta-Burst Transcranial Magnetic Stimulation Alters Electrical Properties of Fast-Spiking Neocortical Interneurons in an Age-Dependent Fashion

Abstract

Modulation of human cortical excitability by repetitive transcranial magnetic stimulation (rTMS) appears to be in part related to changed activity of inhibitory systems. Our own studies showed that intermittent theta-burst stimulation (iTBS) applied via rTMS to rat cortex primarily affects the parvalbumin-expressing (PV) fast-spiking interneurons (FSIs), evident via a strongly reduced PV expression. We further found the iTBS effect on PV to be age-dependent since no reduction in PV could be induced before the perineuronal nets (PNNs) of FSIs start to grow around postnatal day (PD) 30. To elucidate possible iTBS-induced changes in the electrical properties of FSIs and cortical network activity during cortical critical period, we performed ex vivo—in vitro whole-cell patch clamp recordings from pre-labeled FSIs in the current study. FSIs of verum iTBS-treated rats displayed a higher excitability than sham-treated controls at PD29–38, evident as higher rates of induced action potential firing at low current injections (100–200 pA) and a more depolarized resting membrane potential. This effect was absent in younger (PD26–28) and older animals (PD40–62). Slices of verum iTBS-treated rats further showed higher rates of spontaneous excitatory postsynaptic currents (sEPSCs). Based on these and previous findings we conclude that FSIs are particularly sensitive to TBS during early cortical development, when FSIs show an activity-driven step of maturation which is paralleled by intense growth of the PNNs and subsequent closure of the cortical critical period. Although to be proven further, rTMS may be a possible early intervention to compensate for hypo-activity related mal-development of cortical neuronal circuits.

Low-intensity repetitive magnetic stimulation lowers action potential threshold and increases spike firing in layer 5 pyramidal neurons in vitro

“…The LI-rMS protocol delivered was iTBS (Huang et al,145 2005) ( Our results are in part, similar to a recent study using 346 high-intensity rTMS (Hoppenrath et al, 2016 synaptic (Labedi et al, 2014;Lenz et al, 2016) or direct 362 activation (Lenz et al, 2016 (Hensch, 2004 …”

Low‐intensity transcranial magnetic stimulation promotes the survival and maturation of newborn oligodendrocytes in the adult mouse brain

“…Repetitive transcranial magnetic stimulation (rTMS) is a safe and noninvasive form of neural stimulation that applies focal magnetic fields to generate electric currents in the brain (Barker, Freeston, Jalinous, Merton, & Morton, ) and can increase or decrease neuronal firing depending on the intensity, frequency, and pattern of stimulation (Hoppenrath, Hartig, & Funke, ; Müller‐Dahlhaus & Vlachos, ; Tang, Thickbroom, & Rodger, ). rTMS exerts this effect on neuronal activity by modulating the activity of gamma‐aminobutyric acid (GABA)‐ and glutamate‐releasing neurons (Croarkin et al, ; Hoppenrath & Funke, ; Lenz et al, ; Lenz et al, ; Vlachos et al, ), increasing intracellular calcium levels (Grehl et al, ) and promoting the release of growth factors such as brain‐derived neurotrophic factor (BDNF) (Castillo‐Padilla & Funke, ; Makowiecki, Harvey, Sherrard, & Rodger, ; Müller, Toschi, Kresse, Post, & Keck, ; Zhang, Xing, Wang, Tao, & Cheng, )—all of which are key regulators of oligodendrogenesis and adaptive myelination (Gautier et al, ; Hamilton et al, ; Pitman & Young, ; Wong, Xiao, Kemper, Kilpatrick, & Murray, ; Xiao et al, ).…”

Low intensity repetitive transcranial magnetic stimulation modulates skilled motor learning in adult mice

“…Similar to outcomes in humans, iTBS in rodents at high intensities has been shown to induce neural plasticity in the motor cortex using several outcome measures including increased motor evoked potential amplitudes 8 , changes in sensory-motor learning 9 and in immediate early gene expression 10 . Potential mechanisms of iTBS induced plasticity in rodents come from histological and molecular studies, which suggest alterations in both excitatory and inhibitory activity 11 – 14 and changes in brain derived neurotrophic factor (BDNF) expression 15 . A limitation of current rodent rTMS studies is the use of existing stimulator coils that are larger than the rodent brain, resulting in high intensity (HI; e.g.…”