Repetitive Magnetic Stimulation Induces Functional and Structural Plasticity of Excitatory Postsynapses in Mouse Organotypic Hippocampal Slice Cultures

Vlachos, Andreas; Müller‐Dahlhaus, Florian; Rosskopp, J.; Lenz, Maximilian; Ziemann, Ulf; Deller, Thomas

doi:10.1523/jneurosci.0409-12.2012

Cited by 190 publications

(215 citation statements)

References 59 publications

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“…Our result that spine density was not significantly altered is in agreement with a previous study, showing no change in spine density in CA1 pyramidal neurons following a single rTMS stimulation 2 . However, it is surprising that dendritic spine density remains unaffected after long-term stimulation, given our previous results using the same stimulation parameters, demonstrating structural reorganisation in abnormal axon terminals following multiple, but not single rTMS stimulation sessions 19 .…”

Section: Discussionsupporting

confidence: 94%

“…This is consistent with post-mortem studies showing an initial period of apparent spine stability, followed by a detectable increase in density. The possibility that rTMS changes spine dynamics, as opposed to density, is further supported by an increase in the size of small spines following a single stimulation, which the authors suggested may indicate the activation of silent synapses by membrane recruitment of AMPA receptors, precluding the need for de novo synapse generation 2 . Future live imaging studies of spine dynamics in animals that have received single or multiple rTMS stimulation, potentially in combination with learning tasks will provide much needed insight into the mechanisms underpinning the plastic changes elicited by rTMS in humans.…”

Section: Discussionmentioning

confidence: 98%

“…Importantly, rTMS induces long term potentiation (LTP) in rodent hippocampus in vitro 2 and several sessions of high-frequency rTMS increases the capacity to induce LTP (metaplasticity) compared to untreated controls 3, 4 . Because rTMS acts on the same plasticity mechanisms as learning and memory, it has been hypothesised that rTMS may serve as a "priming" mechanism to facilitate long-term synaptic and structural modifications 5, 6 .…”

Section: Introductionmentioning

confidence: 99%

“…To date, the only study to examine changes in dendritic spines after rTMS did so following a single stimulation and showed no change in spine density, although the size of the smallest spines was increased 2 . Therefore, very little has been done to investigate the impact of long term rTMS on spine density in the hippocampus, or how it might interact with the learning process.…”

Section: Introductionmentioning

confidence: 99%

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Long term delivery of pulsed magnetic fields does not improve learning or alter dendritic spine density in the mouse hippocampus

2013

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Repetitive transcranial magnetic stimulation (rTMS) is thought to facilitate brain plasticity. However, few studies address anatomical changes following rTMS in relation to behaviour. We delivered 5 weeks of daily pulsed rTMS stimulation to ephrin-A2 -/- and wildtype mice (n=10 per genotype) undergoing a visual learning task and analysed learning performance, as well as spine density, in the dentate gyrus molecular and CA1 pyramidal cell layers in Golgi-stained brain sections. We found that neither learning behaviour, nor hippocampal spine density was affected by long term rTMS. Our negative results highlight the lack of deleterious side effects in normal subjects and are consistent with previous studies suggesting that rTMS has a bigger effect on abnormal or injured brain substrates than on normal/control structures.

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Section: Discussionsupporting

confidence: 94%

Section: Discussionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Long term delivery of pulsed magnetic fields does not improve learning or alter dendritic spine density in the mouse hippocampus

2013

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“…A human study confirmed that after‐effects of rTMS (theta burst stimulation) are linked to the function of the NMDAR 44. Moreover, animal and behavioral studies45, 46, 47, 48, 49 provide compelling evidence that rTMS alters synaptic plasticity of hippocampal areas. Thus, rTMS may be used in order to improve hippocampal function and increase neuronal NMDAR expression.…”

Section: Discussionmentioning

confidence: 82%

Altered paired associative stimulation‐induced plasticity in NMDAR encephalitis

Volz

Finke

Harms

et al. 2016

Ann Clin Transl Neurol

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ObjectiveTo determine whether neurophysiological mechanisms indicating cortical excitability, long‐term potentiation (LTP)‐like plasticity, GABAergic and glutamatergic function are altered in patients with anti‐N‐methyl‐d‐aspartate receptor (NMDAR) encephalitis and whether they can be helpful as markers of diagnostic assessment, disease progression, and potentially therapy response.MethodsNeurophysiological characterizations of patients with NMDAR encephalitis (n = 34, mean age: 28 ± 11 years; 30 females) and age/gender‐matched healthy controls (n = 27, 28.5 ± 10 years; 25 females) were performed using transcranial magnetic stimulation‐derived protocols including resting motor threshold, recruitment curve, intracortical facilitation, short intracortical inhibition, and cortical silent period. Paired associative stimulation (PAS) was applied to assess LTP‐like mechanisms which are mediated through NMDAR. Moreover, resting state functional connectivity was determined using functional magnetic resonance imaging.Results PAS‐induced plasticity differed significantly between groups (P = 0.0056). Cortical excitability, as assessed via motor‐evoked potentials after PAS, decreased in patients, whereas it increased in controls indicating malfunctioning of NMDAR in encephalitis patients. Lower PAS‐induced plasticity significantly correlated with the modified Rankin Scale (mRS) (r = −0.41; P = 0.0031) and was correlated with lower functional connectivity within the motor network in NMDAR encephalitis patients (P < 0.001, uncorrected). Other neurophysiological parameters were not significantly different between groups. Follow‐up assessments were available in six patients and demonstrated parallel improvement of PAS‐induced plasticity and mRS.InterpretationAssessment of PAS‐induced plasticity may help to determine NMDAR dysfunction and disease severity in NMDAR encephalitis, and might even aid as a sensitive, noninvasive, and well‐tolerated “electrophysiological biomarker” to monitor therapy response in the future.Clinical Trial RegistrationClinicalTrials.gov: Identifier: NCT01865578

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Constitutive tumor necrosis factor (TNF)‐deficiency causes a reduction in spine density in mouse dentate granule cells accompanied by homeostatic adaptations of spine head size

Smilovic

Rietsche

Drakew

et al. 2021

J of Comparative Neurology

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The majority of excitatory synapses terminating on cortical neurons are found on dendritic spines. The geometry of spines, in particular the size of the spine head, tightly correlates with the strength of the excitatory synapse formed with the spine. Under conditions of synaptic plasticity, spine geometry may change, reflecting functional adaptations. Since the cytokine tumor necrosis factor (TNF) has been shown to influence synaptic transmission as well as Hebbian and homeostatic forms of synaptic plasticity, we speculated that TNF‐deficiency may cause concomitant structural changes at the level of dendritic spines. To address this question, we analyzed spine density and spine head area of Alexa568‐filled granule cells in the dentate gyrus of adult C57BL/6J and TNF‐deficient (TNF‐KO) mice. Tissue sections were double‐stained for the actin‐modulating and plasticity‐related protein synaptopodin (SP), a molecular marker for strong and stable spines. Dendritic segments of TNF‐deficient granule cells exhibited ∼20% fewer spines in the outer molecular layer of the dentate gyrus compared to controls, indicating a reduced afferent innervation. Of note, these segments also had larger spines containing larger SP‐clusters. This pattern of changes is strikingly similar to the one seen after denervation‐associated spine loss following experimental entorhinal denervation of granule cells: Denervated granule cells increase the SP‐content and strength of their remaining spines to homeostatically compensate for those that were lost. Our data suggest a similar compensatory mechanism in TNF‐deficient granule cells in response to a reduction in their afferent innervation.

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Repetitive Magnetic Stimulation Induces Functional and Structural Plasticity of Excitatory Postsynapses in Mouse Organotypic Hippocampal Slice Cultures

Cited by 190 publications

References 59 publications

Long term delivery of pulsed magnetic fields does not improve learning or alter dendritic spine density in the mouse hippocampus

Long term delivery of pulsed magnetic fields does not improve learning or alter dendritic spine density in the mouse hippocampus

Altered paired associative stimulation‐induced plasticity in NMDAR encephalitis

Constitutive tumor necrosis factor (TNF)‐deficiency causes a reduction in spine density in mouse dentate granule cells accompanied by homeostatic adaptations of spine head size

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