Dose-Dependence of Changes in Cortical Protein Expression Induced with Repeated Transcranial Magnetic Theta-Burst Stimulation in the Rat

Volz, Lukas J.; Benali, Alia; Mix, Annika; Neubacher, Ute; Funke, Klaus

doi:10.1016/j.brs.2013.01.008

Cited by 83 publications

(92 citation statements)

References 37 publications

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“…Therefore, our data show for the first time that circuit reorganization can occur in the absence of induced spiking activity, which is thought to be the primary mechanism underlying rTMS network effects (Thickbroom, 2007;Benali et al, 2011;Volz et al, 2013). Such network changes in the absence of induced neuronal firing is consistent with the frequency-specific changes to EEG waves reported for very-low-intensity magnetic stimulation (Di Lazzaro et al, 2013).…”

Section: Potential Mechanisms Underlying Effects Of Low-intensity Magsupporting

confidence: 87%

“…Above 10 kHz, there was no detectable acoustic energy emitted above background, which averaged 9 dB SPL from 10 to 20 kHz (measured with the LI-rTMS device turned off). This sound intensity (Ͻ7 dB in the frequency range detectable by mice) is below the auditory threshold (30 dB) for wild-type (Fernandez et al, 2010) and ephrin-A2A5 Ϫ/Ϫ mice (Yates et al, 2014). Therefore, consistent with the low stimulation intensity and lack of auditory or heat/tactile confounders, mice did not display any gross motor, visuomotor, or behavioral response to either the stimulation or sham procedure.…”

Section: Subjects and Housing Ephrin-a2a5mentioning

confidence: 63%

“…Our LI-rTMS stimulation was subthreshold, estimated to be 0.5 V/m (Martiny et al, 2010), which is several orders of magnitude below the ϳ50 V/m that depolarizes neurons (Volz et al, 2013). Therefore, our data show for the first time that circuit reorganization can occur in the absence of induced spiking activity, which is thought to be the primary mechanism underlying rTMS network effects (Thickbroom, 2007;Benali et al, 2011;Volz et al, 2013).…”

Section: Potential Mechanisms Underlying Effects Of Low-intensity Magmentioning

confidence: 67%

“…In addition, because we show that low-intensity pulsed magnetic fields of similar intensity to those delivered outside of the focal area of stimulation in human rTMS (Wagner et al, 2009) affects neuronal circuits, our study may have implications for understanding mechanisms underlying rTMS clinical effects. However, because our device delivers very different stimulation parameters compared with those typically used in human rTMS/ TMS (Wagner et al, 2009;Pell et al, 2011), our data should not be extrapolated directly to a clinical context.…”

Section: Potential Mechanisms Underlying Effects Of Low-intensity Magmentioning

confidence: 87%

“…However, the induced field is not restricted to the target region of rTMS: perifocal areas also receive stimulation, albeit at lower intensities, below the neuron firing threshold (Wagner et al, 2009). Although the functional importance of this perifocal subthreshold stimulation is unclear, it may contribute to network-wide effects.…”

Section: Introductionmentioning

confidence: 99%

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Low-Intensity Repetitive Transcranial Magnetic Stimulation Improves Abnormal Visual Cortical Circuit Topography and Upregulates BDNF in Mice

Makowiecki¹,

Harvey

Sherrard

et al. 2014

Journal of Neuroscience

107

142

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Repetitive transcranial magnetic stimulation (rTMS) is increasingly used as a treatment for neurological and psychiatric disorders.Although the induced field is focused on a target region during rTMS, adjacent areas also receive stimulation at a lower intensity and the contribution of this perifocal stimulation to network-wide effects is poorly defined. Here, we examined low-intensity rTMS (LI-rTMS)-induced changes on a model neural network using the visual systems of normal (C57Bl/6J wild-type, n ϭ 22) and ephrin-A2A5 In the corticotectal efferents, LI-rTMS improved topography of the most abnormal TZs in ephrin-A2A5Ϫ/Ϫ mice without altering topographically normal TZs. To investigate a possible molecular mechanism for LI-rTMS-induced structural plasticity, we measured brain derived neurotrophic factor (BDNF) in the visual cortex and superior colliculus after single and multiple stimulations. BDNF was upregulated after a single stimulation for all groups, but only sustained in the superior colliculus of ephrin-A2A5 Ϫ/Ϫ mice. Our results show that LI-rTMS upregulates BDNF, promoting a plastic environment conducive to beneficial reorganization of abnormal cortical circuits, information that has important implications for clinical rTMS.

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Section: Potential Mechanisms Underlying Effects Of Low-intensity Magsupporting

confidence: 87%

Section: Subjects and Housing Ephrin-a2a5mentioning

confidence: 63%

Section: Potential Mechanisms Underlying Effects Of Low-intensity Magmentioning

confidence: 67%

Section: Potential Mechanisms Underlying Effects Of Low-intensity Magmentioning

confidence: 87%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Low-Intensity Repetitive Transcranial Magnetic Stimulation Improves Abnormal Visual Cortical Circuit Topography and Upregulates BDNF in Mice

Makowiecki¹,

Harvey

Sherrard

et al. 2014

Journal of Neuroscience

107

142

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Reduction in cortical parvalbumin expression due to intermittent theta‐burst stimulation correlates with maturation of the perineuronal nets in young rats

Mix

Hoppenrath

Funke

2014

Developmental Neurobiology

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We recently showed that intermittent theta-burst stimulation (iTBS) using transcranial magnetic stimulation strongly reduces the number of rat neocortical interneurons expressing glutamic acid decarboxylase 67 kDa (GAD67) and parvalbumin (PV), indicating changed activity of fast-spiking (FS) interneurons. In advance of in vitro studies intended to characterize changes in electrical properties of FS interneurons under these conditions, we tested whether the iTBS effect is age-dependent. Conscious Sprague-Dawley rats aged between 28 and 90 days received three blocks of iTBS at 15 min intervals. We found that iTBS-related reduction in PV+ cells was absent up to an age of 32 days, then gradually increased, and approached a maximum of about 40% reduction at an age of about 40 days. The relative number of cells expressing PV (PV+, 8-9%) did not change with age in sham-controls and also the increase in cortical c-Fos expression induced by iTBS was not principally age-dependent. However, a prominent growth of the perineuronal nets, typically surrounding the PV+ cells, exactly paralleled the increase in the iTBS effect. Based on these findings, we conclude that the functional development of the inhibitory network of PV+ interneurons with regard to intracortical synaptic connectivity is not sufficiently matured in rats younger than 35 d to enable activity-dependent modifications during iTBS. Outgrowth of the perineuronal nets and associated maturation of excitatory cortical inputs, as is characteristic for the critical cortical period, may take place before PV+ interneurons can be sufficiently activated via repetitive transcranial magnetic stimulation, allowing plastic changes of molecular phenotype and likely also synaptic plasticity.

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Effects of chronic iTBS‐rTMS and enriched environment on visual cortex early critical period and visual pattern discrimination in dark‐reared rats

Castillo-Padilla

Funke

2015

Developmental Neurobiology

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Early cortical critical period resembles a state of enhanced neuronal plasticity enabling the establishment of specific neuronal connections during first sensory experience. Visual performance with regard to pattern discrimination is impaired if the cortex is deprived from visual input during the critical period. We wondered how unspecific activation of the visual cortex before closure of the critical period using repetitive transcranial magnetic stimulation (rTMS) could affect the critical period and the visual performance of the experimental animals. Would it cause premature closure of the plastic state and thus worsen experience-dependent visual performance, or would it be able to preserve plasticity? Effects of intermittent theta-burst stimulation (iTBS) were compared with those of an enriched environment (EE) during dark-rearing (DR) from birth. Rats dark-reared in a standard cage showed poor improvement in a visual pattern discrimination task, while rats housed in EE or treated with iTBS showed a performance indistinguishable from rats reared in normal light/dark cycle. The behavioral effects were accompanied by correlated changes in the expression of brain-derived neurotrophic factor (BDNF) and atypical PKC (PKCζ/PKMζ), two factors controlling stabilization of synaptic potentiation. It appears that not only nonvisual sensory activity and exercise but also cortical activation induced by rTMS has the potential to alleviate the effects of DR on cortical development, most likely due to stimulation of BDNF synthesis and release. As we showed previously, iTBS reduced the expression of parvalbumin in inhibitory cortical interneurons, indicating that modulation of the activity of fast-spiking interneurons contributes to the observed effects of iTBS.

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Dose-Dependence of Changes in Cortical Protein Expression Induced with Repeated Transcranial Magnetic Theta-Burst Stimulation in the Rat

Cited by 83 publications

References 37 publications

Low-Intensity Repetitive Transcranial Magnetic Stimulation Improves Abnormal Visual Cortical Circuit Topography and Upregulates BDNF in Mice

Low-Intensity Repetitive Transcranial Magnetic Stimulation Improves Abnormal Visual Cortical Circuit Topography and Upregulates BDNF in Mice

Reduction in cortical parvalbumin expression due to intermittent theta‐burst stimulation correlates with maturation of the perineuronal nets in young rats

Effects of chronic iTBS‐rTMS and enriched environment on visual cortex early critical period and visual pattern discrimination in dark‐reared rats

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