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

Brita Fritsch; Janine Reis; Keri Martinowich; Heidi M. Schambra; Yuanyuan Ji; Leonardo G. Cohen; Bai Lu

doi:10.1016/j.neuron.2010.03.035

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

Brita Fritsch, Janine Reis, Keri Martinowich, Heidi M. Schambra, Yuanyuan Ji, Leonardo G. Cohen, Bai Lu

Research output: Contribution to journal › Article › peer-review

798 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	198-204
Number of pages	7
Journal	Neuron
Volume	66
Issue number	2
DOIs	https://doi.org/10.1016/j.neuron.2010.03.035
State	Published - Apr 2010
Externally published	Yes

Keywords

Signaling
Sysneuro

ASJC Scopus subject areas

General Neuroscience

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10.1016/j.neuron.2010.03.035

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@article{b20eb98194bb455982f44215ae5a4164,

title = "Direct current stimulation promotes BDNF-dependent synaptic plasticity: Potential implications for motor learning",

abstract = "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.",

keywords = "Signaling, Sysneuro",

author = "Brita Fritsch and Janine Reis and Keri Martinowich and Schambra, {Heidi M.} and Yuanyuan Ji and Cohen, {Leonardo G.} and Bai Lu",

note = "Funding Information: This research was supported by the NINDS Intramural Research Program, NIH (B.F., J.R., H.M.S.), and the Alexander von Humboldt Foundation Germany (J.R.). We thank J.W. Krakauer and P.A. Celnik for helpful comments and for their involvement in the previous characterization of the motor task utilized. We thank F. Lee, A. Morozov, and D. Ginty (transgenic animals), D. Ide and A. Mitz (field measurements), and D. Brandsch and K. Spies (data analysis). ",

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T2 - Potential implications for motor learning

AU - Fritsch, Brita

AU - Reis, Janine

AU - Martinowich, Keri

AU - Schambra, Heidi M.

AU - Ji, Yuanyuan

AU - Cohen, Leonardo G.

AU - Lu, Bai

N1 - Funding Information: This research was supported by the NINDS Intramural Research Program, NIH (B.F., J.R., H.M.S.), and the Alexander von Humboldt Foundation Germany (J.R.). We thank J.W. Krakauer and P.A. Celnik for helpful comments and for their involvement in the previous characterization of the motor task utilized. We thank F. Lee, A. Morozov, and D. Ginty (transgenic animals), D. Ide and A. Mitz (field measurements), and D. Brandsch and K. Spies (data analysis).

PY - 2010/4

Y1 - 2010/4

N2 - 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.

AB - 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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KW - Sysneuro

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

Abstract

Keywords

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