Repetitive magnetic stimulation induces plasticity of inhibitory synapses

Lenz, Maximilian; Galanis, Christos; Müller‐Dahlhaus, Florian; Opitz, Alexander; Wierenga, Corette J.; Szabó, Gábor; Ziemann, Ulf; Deller, Thomas; Funke, Klaus; Vlachos, Andreas

doi:10.1038/ncomms10020

Cited by 151 publications

(135 citation statements)

References 72 publications

(133 reference statements)

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“…Based on these results we conclude that rMS induces calcium-dependent phosphorylation/dephosphorylation reactions, which destabilize gephyrin scaffolds and thereby mediate a long-term depression of GABAergic neurotransmission. In our experimental setting tonic inhibition, mediated by extrasynaptic GABA receptors, was not affected by rMS (Lenz et al, 2016).…”

Section: Rtms-induced Long-term Depression Of Inhibitory Synapsesmentioning

confidence: 89%

“…Interestingly our experiments show that both processes are calcium-dependent and require the activation of NMDA receptors and L-type voltage-gated calcium channels (Vlachos et al, 2012;Lenz et al, 2015Lenz et al, , 2016. Based on this observation, the question arises how rTMS-induced inhibitory and excitatory synaptic modifications interact with each other (at the temporal, spatial and molecular level).…”

Section: Interactions Of Rtms-induced Inhibitory and Excitatory Synapmentioning

confidence: 99%

“…3): 10 Hz rMS mainly affects dendritic but not somatic inhibition (Lenz et al, 2016). In turn, the same stimulation protocol results in potentiation of excitatory synapses on small dendritic spines close to the soma of pyramidal neurons (Vlachos et al, 2012;Lenz et al, 2015).…”

Section: Synapse-specific Effects Of Rtmsmentioning

confidence: 99%

“…These findings support the hypothesis that plasticity of excitatory synapses is not directly attributed to rTMS. In light of this hypothesis experiments addressing the exact temporal sequence of rTMS-induced long-term depression of inhibitory synapses (Lenz et al, 2016) and of rTMS-induced modification of excitatory synapses (Vlachos et al, 2012) seem crucial. Moreover, studies in which network activity is systematically modulated before, during and after rTMS (e.g.…”

Section: Interactions Of Rtms-induced Inhibitory and Excitatory Synapmentioning

confidence: 99%

“…In a recent study the effects of repetitive magnetic stimulation (rMS) on structural, functional and molecular properties of inhibitory synapses were studied (Lenz at al., 2016). Using single cell recordings of CA1 pyramidal neurons in mouse brain slice cultures, we showed that rMS indeed reduces inhibitory neurotransmission.…”

Section: Rtms-induced Long-term Depression Of Inhibitory Synapsesmentioning

confidence: 99%

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Assessment and modulation of cortical inhibition using transcranial magnetic stimulation

Vlachos¹,

Funke

Ziemann

2017

E-Neuroforum

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Transcranial magnetic stimulation (TMS) is a non-invasive brain stimulation technique, which is used for diagnostic, therapeutic and scientific purposes in the field of neurology and psychiatry. It is based on the physical principle of electromagnetic induction and allows for the local activation of cortical areas through the intact skull of conscious humans. When applied repeatedly (repetitive TMS; rTMS) sustained changes of cortical excitability can be observed. Hence, TMS resembles a promising approach for assessing and modulating neuronal networks in a non-invasive manner. However, despite its broad clinical application, the cellular and molecular mechanisms of rTMS-based therapies remain not well understood. Established therapeutic concepts assume that pathologically altered cortical excitability is normalised, which may involve 'long-term potentiation' or 'long-term depression' of excitatory synapses. Indeed, animal studies demonstrate that rTMS induces long-term changes of excitatory neurotransmission. However, it is unclear through which mechanisms synaptic changes, which are caused by external electromagnetic activation of the cortex and therefore are not specific for context or behaviour, could have a positive impact on complex brain function. More recent findings suggest that not only excitatory but also inhibitory neuronal networks are modulated by rTMS. It was shown for example that 10 Hz rTMS leads to a calcium-dependent long-term depression of inhibitory GABAergic synapses. Since the reduction of inhibitory neurotransmission (= disinhibition) is considered important for the expression of associative plasticity at excitatory synapses, it is conceivable that rTMS-induced disinhibition may promote context-and behaviour-specific synaptic changes. Hence, the model of rTMS-induced local disinhibition represents an attractive explanation for the observation that a seemingly unspecific (exogenous) magnetic stimulation could induce specific (endogenous) structural, functional and molecular changes of cortical synapses. Current research focuses on the effect of rTMSinduced disinhibition on synaptic plasticity in suitable animal models (both in vivo and in vitro). Thus, apart from its diagnostic and therapeutic potential TMS represents a promising method for conducting clinically-oriented translational plasticity studies.

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Section: Rtms-induced Long-term Depression Of Inhibitory Synapsesmentioning

confidence: 89%

Section: Interactions Of Rtms-induced Inhibitory and Excitatory Synapmentioning

confidence: 99%

Section: Synapse-specific Effects Of Rtmsmentioning

confidence: 99%

Section: Interactions Of Rtms-induced Inhibitory and Excitatory Synapmentioning

confidence: 99%

Section: Rtms-induced Long-term Depression Of Inhibitory Synapsesmentioning

confidence: 99%

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Assessment and modulation of cortical inhibition using transcranial magnetic stimulation

Vlachos¹,

Funke

Ziemann

2017

E-Neuroforum

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The microbiota‐gut‐brain axis and epilepsy from a multidisciplinary perspective: Clinical evidence and technological solutions for improvement of in vitro preclinical models

Fusco

Perottoni

Giordano

et al. 2022

Bioengineering & Transla Med

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Epilepsy is a common neurological disease characterized by the enduring predisposition of the brain to generate seizures. Among the recognized causes, a role played by the gut microbiota in epilepsy has been hypothesized and supported by new investigative approaches. To dissect the microbiota‐gut‐brain (MGB) axis involvement in epilepsy, in vitro modeling approaches arouse interest among researchers in the field. This review summarizes, first of all, the evidence of a role of the MGB axis in epilepsy by providing an overview of the recent clinical and preclinical studies and showing how dietary modification, microbiome supplementations, and hence, microbiota alterations may have an impact on seizures. Subsequently, the currently available strategies to study epilepsy on animal and in vitro models are described, focusing attention on these latter and the technological challenges for integration with already existing MGB axis models. Finally, the implementation of existing epilepsy in vitro systems is discussed, offering a complete overview of the available technological tools which may improve reliability and clinical translation of the results towards the development of innovative therapeutic approaches, taking advantage of complementary technologies.

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

Cullen

Senesi

Tang

et al. 2019

Glia

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Neuronal activity is a potent extrinsic regulator of oligodendrocyte generation and central nervous system myelination. Clinically, repetitive transcranial magnetic stimulation (rTMS) is delivered to noninvasively modulate neuronal activity; however, the ability of rTMS to facilitate adaptive myelination has not been explored. By performing cre‐lox lineage tracing, to follow the fate of oligodendrocyte progenitor cells in the adult mouse brain, we determined that low intensity rTMS (LI‐rTMS), administered as an intermittent theta burst stimulation, but not as a continuous theta burst or 10 Hz stimulation, increased the number of newborn oligodendrocytes in the adult mouse cortex. LI‐rTMS did not alter oligodendrogenesis per se, but instead increased cell survival and enhanced myelination. These data suggest that LI‐rTMS can be used to noninvasively promote myelin addition to the brain, which has potential implications for the treatment of demyelinating diseases such as multiple sclerosis.

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Repetitive magnetic stimulation induces plasticity of inhibitory synapses

Cited by 151 publications

References 72 publications

Assessment and modulation of cortical inhibition using transcranial magnetic stimulation

Assessment and modulation of cortical inhibition using transcranial magnetic stimulation

The microbiota‐gut‐brain axis and epilepsy from a multidisciplinary perspective: Clinical evidence and technological solutions for improvement of in vitro preclinical models

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

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