Direct current stimulation promotes BDNF-dependent synaptic plasticity: Potential implications for motor learning

By B. Fritsch, Janine Reis, Keri Martinowich, Heidi M. Schambra, Yuanyuan Ji, Leonardo G. Cohen, B. Lu. Neuron, 2010

1,379 citations recorded by the source corpus.

SUMMARY Despite its increasing use in experimental and clinical settings, the cellular and molecular mechanisms underlying transcranial direct current stimulation (tDCS) remain unknown. Anodal tDCS applied to human motor cortex (M1) improves motor skill learning. Here, we demonstrate in mouse M1 slices that DCS induces a long-lasting synaptic potentiation (DCS-LTP), which is polarity-specific, NMDA-receptor dependent and requires coupling of DCS with repetitive low-frequency synaptic activation (LFS). Combined DCS and LFS enhance BDNF-secretion and TrkB-activation, and DCS-LTP is absent in BDNF and TrkB mutant mice, suggesting that BDNF is a key mediator of this phenomenon. Moreover, the BDNF val66met polymorphism known to partially affect activity-dependent BDNF secretion impairs motor skill acquisition in humans and mice. Motor learning is enhanced by anodal tDCS, as long as activity-dependent BDNF secretion is in place. We propose that tDCS may improve motor skill learning through augmentation of synaptic plasticity that requires BDNF-secretion and TrkB-activation within M1.

Subfields: Cellular and Molecular Neuroscience, Neurology

View Paper: https://www.semanticscholar.org/paper/70b5249a7a3e0e61b0c0514633fe46b9e4a11a28

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Citations in the corpus

Dissociating the roles of the cerebellum and motor cortex during adaptive learning: the motor cortex retains what the cerebellum learns. (2011, background): “A recent study by Fritsch et al. (2010) has shown that the cellular mechanisms underlying anodal direct current stimulation include an enhanced secretion of the neurotrophin brainderived neurotrophic factor (BDNF) and increased activation of the high-affinity tyrosine kinase receptors (TrkB).”
tDCS-enhanced motor and cognitive function in neurological diseases (2014, positive): “Previous studies have demonstrated differential responses to both TMS and tDCS in carriers of the BDNF Val66Met polymorphism in the motor system (see for example (Cheeran et al., 2008; Fritsch et al., 2010; Witte et al., 2012).”
Battery powered thought: Enhancement of attention, learning, and memory in healthy adults using transcranial direct current stimulation (2014, neutral): “Stimulation parameters were similar between these two studies, but stimulus durationwas longer (30 vs. 20 min) and sample sizewas smaller in the Galea and Celnik (2009) study (N = 9) compared to the study by Reis et al. (2009) (N = 24).”
A technical guide to tDCS, and related non-invasive brain stimulation tools (2015, background): “In analogy to pharmacological neuromodulators, tDCS does not induce activity in resting neuronal networks, but modulates spontaneous neuronal activity (Fritsch et al., 2010).”
Low intensity transcranial electric stimulation: Safety, ethical, legal regulatory and application guidelines (2017, background): “, 2009), but likely modify spontaneous firing rates and ongoing processes such as plasticity that are sensitive to polarization levels (Fritsch et al., 2010; Jackson et al., 2016; Ranieri et al., 2012), and over time may induce molecular or structural changes.”
Neuroplasticity subserving motor skill learning (2011, positive): “These findings led to the hypothesis that the presence of this particular polymorphism could influence motor skill learning (Fritsch et al., 2010).”
Determinants of the induction of cortical plasticity by non‐invasive brain stimulation in healthy subjects (2010, background): “However, a very recent study (Fritsch et al. 2010) used a mouse motor cortex slice preparation to study the response to anodal tDCS.”
Clinical Research with Transcranial Direct Current Stimulation (tDCS): Challenges and Future Directions (2011, neutral): “A recent study showed BDNF expression also increases after tDCS.(8) Additional biomarkers used in neuropsychiatry include inflammatory proteins such as interleucin-1, interleucin-6, and TNF-alpha(137); hypothalamic-pituitary-adrenal activity, which is measured by serum and salivary cortisol(138); an”