Abstract There is evidence that transcranial direct current stimulation can boost learning performance. Arguably, this boost is related to synaptic plasticity. However, the precise effects on synaptic plasticity and its underlying mechanisms are not known. We hypothesized that direct current stimulation modulates endogenous Hebbian plasticity mechanisms due to its ability to polarize cellular membrane. To test this we induced long term plasticity (LTP) using theta-burst stimulation (TBS) in rat hippocampus, and measured the effects of concurrent direct current stimulation (DCS). Soma-depolarizing DCS increased TBS-induced LTP. Oscillating current stimulation is equally effective provided the soma-depolarizing phase is time-aligned with the theta-bursts, suggesting that only instantaneous depolarization is relevant. Importantly, the effect is pathway-specific and associative. These findings are consistent with classic theory on the role of post-synaptic membrane potential in Hebbian plasticity. These data suggest that the effects of direct current stimulation are specific because they modulate endogenous Hebbian plasticity, thus inheriting its exquisite functional specificity.

Direct current stimulation boosts associative Hebbian synaptic plasticity and maintains its pathway specificity