Direct Current Stimulation Modulates LTP and LTD: Activity Dependence and Dendritic Effects

Abstract

Background Transcranial direct current stimulation (tDCS) has been reported to improve various forms of learning in humans. Stimulation is often applied during training, producing lasting enhancements that are specific to the learned task. These learning effects are thought to be mediated by altered synaptic plasticity. However, the effects of DCS during the induction of endogenous synaptic plasticity remain largely unexplored. Objective/Hypothesis Here we are interested in the effects of DCS applied during synaptic plasticity induction. Methods To model endogenous plasticity we induced long-term potentiation (LTP) and depression (LTD) at Schaffer collateral synapses in CA1 of rat hippocampal slices. Anodal and cathodal DCS at 20 V/m were applied throughout plasticity induction in both apical and basal dendritic compartments. Results When DCS was paired with concurrent plasticity induction, the resulting plasticity was biased towards potentiation, such that LTP was enhanced and LTD was reduced. Remarkably, both anodal and cathodal stimulation can produce this bias, depending on the dendritic location and type of plasticity induction. Cathodal DCS enhanced LTP in apical dendrites while anodal DCS enhanced LTP in basal dendrites. Both anodal and cathodal DCS reduced LTD in apical dendrites. DCS did not affect synapses that were weakly active or when NMDA receptors were blocked. Conclusions These results highlight the role of DCS as a modulator, rather than inducer of synaptic plasticity, as well as the dependence of DCS effects on the spatial and temporal properties of endogenous synaptic activity. The relevance of the present results to human tDCS should be validated in future studies.