Direct current stimulation boosts hebbian plasticity in vitro

Abstract

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.

Modulation of solute diffusivity in brain tissue as a novel mechanism of transcranial direct current stimulation (tDCS)

“…These findings imply that tDCS can change the microenvironment surrounding neurons, glial cells and vasculature to achieve its therapeutic effects – though such links remain to be established. Given the universal role of ECS in brain function, this motion of action complementary to standard neurophysiological outcomes of tDCS including altered excitability 49 , 72 , 73 and synaptic plasticity 14 , 19 , 74 , 75 , as well as reported morphological and molecular changes 76 , 77 . Finally, these findings also suggest that tDCS can be applied to enhance the drug brain delivery, especially macromolecules, through the non-invasive route from the BBB and the minimum-invasive route by CSF if injected through brain ventricles and spinal cord.…”

“…Transcranial direct current stimulation (tDCS) generates static electric fields in the brain leading to lasting changes in brain function 1 – 4 . The breadth of applications tDCS is investigated for 5 – 8 suggests a mechanism of action that is on the one hand generalizable 9 – 11 while on the other hand tunable to specific outcomes 12 – 14 . As with other forms of neuromodulation 15 , 16 , research on tDCS cellular mechanisms has focused on characterizing which neuronal elements are activated 9 , 17 – 19 , which has been extended to consider additional cells types notably glial 20 , 21 and endothelial cells 22 , 23 .…”

Efficacy of Noninvasive Brain Stimulation (tDCS or TMS) Paired with Language Therapy in the Treatment of Primary Progressive Aphasia: An Exploratory Meta-Analysis

“…We hypothesize that a greater therapeutic benefit would be driven by tDCS compared to TMS when paired with language therapy. Our rationale for making this prediction is that because tDCS induces sub-threshold stimulation, its effects may be preferentially driven by behaviorally mediated state-dependent activation of relevant networks than supra-threshold stimulation induced by TMS [55,56]. As such, we reasoned that tDCS might be more effective when paired with behavioral language therapies than TMS.…”

Group and Individual Level Variations between Symmetric and Asymmetric DLPFC Montages for tDCS over Large Scale Brain Network Nodes

“…1-2 mA) from an anode to a cathode electrode at specific scalp locations [1][2][3]. Neuromodulation effects of tDCS are electrode position (montage) specific and are understood to reflect a combination of different mechanisms of action from the cellular [4][5][6][7] to the large-scale functional network scale [8][9][10][11].…”