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

- tDCS can improve learning outcomes when paired with various training paradigms, but the mechanisms for this remain unknown.
- Here we show that DCS facilitates LTP and diminishes LTD in hippocampal slices.
- These effects can be polarity independent, as both anodal and cathodal DCS can produce similar modulation of plasticity.
- Outcomes depended on dendritic location and endogenous synaptic activity.
- These results motivate an approach to tDCS protocol design that considers these factors.

BackgroundTranscranial 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/HypothesisHere we are interested in the effects of DCS applied during synaptic plasticity induction.MethodsTo 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.ResultsWhen 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.ConclusionsThese 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.