Direct Current Stimulation Promotes BDNF-Dependent Synaptic Plasticity: Potential Implications for Motor Learning
Open accessAbstract
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 the 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.
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Changes in cortical excitability and improvements in behavior induced by tDCS have been reported to persist long after the stimulation period.
“Importantly, changes in cortical excitability and improvements in behavior induced by tDCS have been reported to persist long after the stimulation period [25–28].”
From Primary outcome from the augmenting cognitive training in older adults study (ACT): A tDCS and cognitive training randomized clinical trial (2023) · cites this paper as [27]
Direct current stimulation promotes learning in homozygous BDNF val/val subjects but not in met allele carriers, both in humans and mice.
“Consistent with this, direct current stimulation promotes learning in homozygous BDNF val/val subjects, but not in met allele carriers, both in humans and mice76.”
From Neuronal plasticity and neurotrophic factors in drug responses (2017) · cites this paper as [76]
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- Authors
- Fritsch, B., Reis, J., Martinowich, K., Schambra, H. M., Ji, Y., Cohen, L. G., & Lu, B.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Cohen, Leonardo G.
- Lu, Bai
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2010-04
- Volume
- 66
- Issue
- 2
- Pages
- 198-204
- ISSN
- 0896-6273 (ISSN-L)
- PMC
- PMC2864780
- OpenAlex
- W2055362996
- Cited by
- 1,420
- References
- 41
- Citations by year
- 2026: 57 · 2025: 75 · 2024: 74 · 2023: 95 · 2022: 110 · 2021: 116 · 2020: 113 · 2019: 83 · 2018: 84 · 2017: 99 · 2016: 106 · 2015: 93 · 2014: 94 · 2013: 93 · 2012: 57
- FWCI
- 42.57
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Alexander von Humboldt-Stiftung
- National Institutes of Health
- National Institute of Neurological Disorders and Stroke
- Topics
- Life Sciences › Neuroscience › Neurology › Transcranial Magnetic Stimulation Studies
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Health Sciences › Medicine › Neurology › Neurological disorders and treatments
- Keywords
- transcranial direct current stimulation, brain-derived neurotrophic factor, TrkB, synaptic plasticity, long-term potentiation, motor cortex, motor learning, NMDA receptor, low-frequency stimulation, BDNF Val66Met polymorphism
- MeSH terms
- Analysis of Variance, Animals, Electric Stimulation, Electrophysiology, Electric Stimulation Therapy, Humans, Learning, Motor Cortex, Motor Skills, Phosphorylation, Synapses, Time Factors, Blotting, Western, Long-Term Potentiation, Mice, Knockout, Brain-Derived Neurotrophic Factor, Excitatory Postsynaptic Potentials, Polymorphism, Single Nucleotide, Receptor, trkB, Rotarod Performance Test, Mice
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