Transcranial Direct Current Stimulation (tDCS) Induces Adrenergic Receptor-Dependent Microglial Morphological Changes in Mice

Mishima, Tatsuya; Nagai, Torao; Yahagi, Kazuko; Akther, Sonam; Oe, Yuki; Monai, Hiromu; Kohsaka, Shinichi; Hirase, Hajime

doi:10.1523/eneuro.0204-19.2019

Cited by 50 publications

(48 citation statements)

References 56 publications

(71 reference statements)

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“…Anodal tDCS actions in glia were further confirmed by Mishima et al [76]. Using a mouse model lacking Ca 2+ uptake in astrocytes, the inositol trisphosphate receptor type 2 (IP3R2) knockout (KO) mouse and also an adrenergic receptor antagonist, they confirmed decreased microglia motility along with soma enlargement in tDCS stimulated animals [76]. In poststroke recovery, it was found that anodal currents significantly increased the GAP-43 and the microtubuleassociated protein 2 (MAP-2) expression around the infarct area [56].…”

Section: Activation Of Neuroplasticity-associated Genementioning

confidence: 64%

“…It was also demonstrated that sensory evoked cortical responses were boosted after tDCS via alpha-1 adrenergic receptormediated astrocytic Ca 2+ /IP3 signaling, thus involving also glia and the adrenergic system [75]. Anodal tDCS actions in glia were further confirmed by Mishima et al [76]. Using a mouse model lacking Ca 2+ uptake in astrocytes, the inositol trisphosphate receptor type 2 (IP3R2) knockout (KO) mouse and also an adrenergic receptor antagonist, they confirmed decreased microglia motility along with soma enlargement in tDCS stimulated animals [76].…”

Section: Activation Of Neuroplasticity-associated Genementioning

confidence: 81%

“…Accordingly, others reported a spatial working memory enhancement after anodal stimulation over left medial PFC that was lost with the administration of the AMPAR antagonist perampanel (PRP). In contrast to cathodal currents, anodal currents enhanced intracellular calcium (Ca 2+ ) intake in cell cultures including astrocytes [74][75][76], a process associated with AMPAR phosphorylation 6 Neural Plasticity 14 Neural Plasticity nd trafficking to postsynaptic density [77] and ultimately, allowing LTP facilitation, a cellular correlate of learning and memory.…”

Section: Effect Of Tdcs On Cellular and Molecular Neuroplasticitymentioning

confidence: 99%

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Memory and Cognition-Related Neuroplasticity Enhancement by Transcranial Direct Current Stimulation in Rodents: A Systematic Review

2020

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Brain stimulation techniques, including transcranial direct current stimulation (tDCS), were identified as promising therapeutic tools to modulate synaptic plasticity abnormalities and minimize memory and learning deficits in many neuropsychiatric diseases. Here, we revised the effect of tDCS on the modulation of neuroplasticity and cognition in several animal disease models of brain diseases affecting plasticity and cognition. Studies included in this review were searched following the terms (“transcranial direct current stimulation”) AND (mice OR mouse OR animal) and according to the PRISMA statement requirements. Overall, the studies collected suggest that tDCS was able to modulate brain plasticity due to synaptic modifications within the stimulated area. Changes in plasticity-related mechanisms were achieved through induction of long-term potentiation (LTP) and upregulation of neuroplasticity-related proteins, such as c-fos, brain-derived neurotrophic factor (BDNF), or N-methyl-D-aspartate receptors (NMDARs). Taken into account all revised studies, tDCS is a safe, easy, and noninvasive brain stimulation technique, therapeutically reliable, and with promising potential to promote cognitive enhancement and neuroplasticity. Since the use of tDCS has increased as a novel therapeutic approach in humans, animal studies are important to better understand its mechanisms as well as to help improve the stimulation protocols and their potential role in different neuropathologies.

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Section: Activation Of Neuroplasticity-associated Genementioning

confidence: 64%

Section: Activation Of Neuroplasticity-associated Genementioning

confidence: 81%

Section: Effect Of Tdcs On Cellular and Molecular Neuroplasticitymentioning

confidence: 99%

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Memory and Cognition-Related Neuroplasticity Enhancement by Transcranial Direct Current Stimulation in Rodents: A Systematic Review

2020

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“…Prolonged stimulation necessarily includes effects operating on both short timescales (membrane polarization, plasticity induction) and longer timescales (cell motility and immune responses), e.g. [81]. However, shortening the stimulation and pairing it with quicker (sub-minute) bouts of training as we have done here, could be a useful strategy to isolate effects based on Hebbian plasticity induction, which operate on faster timescales.…”

Section: Mechanismmentioning

confidence: 97%

Direct current stimulation boosts hebbian plasticity in vitro

et al. 2020

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Background: There is evidence that transcranial direct current stimulation (tDCS) can improve learning performance. Arguably, this effect is related to long term potentiation (LTP), but the precise biophysical mechanisms remain unknown. Hypothesis: We propose that direct current stimulation (DCS) causes small changes in postsynaptic membrane potential during ongoing endogenous synaptic activity. The altered voltage dynamics in the postsynaptic neuron then modify synaptic strength via the machinery of endogenous voltage-dependent Hebbian plasticity. This hypothesis predicts that DCS should exhibit Hebbian properties, namely pathway specificity and associativity. Methods: We studied the effects of DCS applied during the induction of LTP in the CA1 region of rat hippocampal slices and using a biophysical computational model. Results: DCS enhanced LTP, but only at synapses that were undergoing plasticity, confirming that DCS respects Hebbian pathway specificity. When different synaptic pathways cooperated to produce LTP, DCS enhanced this cooperation, boosting Hebbian associativity. Further slice experiments and computer simulations support a model where polarization of postsynaptic pyramidal neurons drives these plasticity effects through endogenous Hebbian mechanisms. The model is able to reconcile several experimental results by capturing the complex interaction between the induced electric field, neuron morphology, and endogenous neural activity. Conclusions: These results suggest that tDCS can enhance associative learning. We propose that clinical tDCS should be applied during tasks that induce Hebbian plasticity to harness this phenomenon, and that the effects should be task specific through their interaction with endogenous plasticity mechanisms. Models that incorporate brain state and plasticity mechanisms may help to improve prediction of tDCS outcomes.

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“…Moreover, the potential effects of transcutaneous stimulation, including TI, may not be limited to neurons. For example, it has been suggested that glial cells may be affected by transcranial electric stimulation (Gellner et al, 2016;Mishima et al, 2019;Ruohonen and Karhu, 2012). Some of these phenomena have been preliminarily explored by Grossman et al, in their safety assessment of TI with no evidence of anatomical side effects (Grossman et al, 2017).…”

Section: Articlementioning

confidence: 99%