Direct current stimulation modulates LTP and protein expression in rat hippocampus.

Introduction: Transcranial direct current stimulation (tDCS) can produce a lasting polarity-specific modulation of cortical excitability in the brain and it is increasingly used in experimental and clinical settings. A large amount of evidence supports the view that the after-effects of tDCS are mediated by the interaction with molecular mechanisms of activity-dependent synaptic plasticity. The level of this interaction is unknown. Some immediate early genes, such as c-fos and zif268, are rapidly induced following neuronal activation and may act as regulators of downstream target genes in coupling short-term events with long-term functional modifications of synaptic function. Objectives: (1) To assess the effect of DCS on the induction of one of the most studied NMDA receptor-dependent forms of long-term potentiation (LTP) of synaptic activity; (2) to shed light on the molecular basis of DCS after-effects. Methods: We investigated the effect of anodal and cathodal DCS, applied to rat brain slices, on LTP induction at CA3-CA1 hippocampal synapses (Shaffer collateral pathway). In the same experimental model, we also explored by immunohistochemistry the effect of DCS on the expression of c-fos and zif268 proteins in CA and DG regions of the hippocampus. Results: DCS determined a bidirectional modulation of LTP, that was increased by anodal and reduced by cathodal DCS. Moreover, we found that both polarities of DCS produce a marked and consistent increase in the expression of zif268 in the CA region of the hippocampus, while the same protocols of stimulation produce a less pronounced increase in c-fos expression, that was observed in both the CA and DG regions. Conclusions: The present data confirm the interaction of DCS with the molecular pathways underlying activity-dependent synaptic plasticity. The modulation of this processes might become of use in neurological diseases to help enhancing the adaptive and suppress the maladaptive forms of brain plasticity.