Transcranial direct current stimulation enhances hippocampal CA1 long-term potentiation via BDNF secretion and TrkB activation

[Speaker] Ting-Hsuan Yu:1
[Co-author] Yi-Jen Wu:2, Kuei-Sen Hsu:1,3
1:Institute of Basic Medical Sciences, Natioanal Cheng Kung University, Taiwan, 2:Department of Neurology, Natioanal Cheng Kung University, Taiwan, 3:Department of Pharmacology, College of Medicine, Natioanal Cheng Kung University, Taiwan

Background: Transcranial direct current stimulation (tDCS) is a non-invasive neuromodulation technique providing a focal polarity-specific direct current electric field, either anodal or cathodal, through the skull to modulate brain function. Although it has been hypothesized that tDCS may elicit its effects by altered synaptic plasticity, there is little information existed about the direct effects of in vivo tDCS on long-term potentiation (LTP), a cellular correlate of learning and memory. The present study is designed to study the cellular and molecular mechanisms underlying the effect of anodal tDCS on the induction of LTP at Schaffer collateral-CA1 synapses in rat hippocampal slices.

Methods: A head electrode of 0.25 cm2 will be applied to the skull over the hippocampus. Anodal tDCS was applied using a constant current stimulator for 30 min at 250 microamp. Extracellular field potential recordings were used to examine the induction of LTP in slices from sham- and tDCS-treated rats. Brain derived neurotrophic factor (BDNF) was measured with ELISA kit and TrkB activation was determined by Western blot analysis.

Results: We found that hippocampal CA1 LTP were enhanced in slices from rats subjected to anodal tDCS over the hippocampus with no significant changes in basal synaptic transmission or paired pulse facilitation. The enhancing effect of tDCS on LTP was still maintained 12 h after tDCS. In addition, ex vivo hippocampal slices from rats that have been subjected to anodal tDCS treatment with the TrkB inhibitor ANA-12, but not D1 receptor antagonist SKF-83566 or beta-adrenergic receptor antagonist propranolol, efficiently inhibited the enhancing effect of tDCS on hippocampal CA1 LTP. The tDCS-treated rats exhibited higher levels of BDNF and TrkB phosphorylation in hippocampal CA1 tissue lysates compared to sham stimulation group.

Conclusions: Our results suggest the importance of BDNF/TrkB-mediated neuroptophic-priming for the facilitating effect of anodal tDCS on the induction of hippocampal CA1 LTP. These findings may serve as an advanced understanding of the neurophysiological basis to optimize the clinical application of tDCS for improving cognitive function.

Funding: This work was supported by research grants from the Ministry of Science and Technology (MOST 106-2321-B-006-018), Taiwan.

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