Direct Current stimulation modulates long-term potentiation (LTP) and zif 268 Expression in rat hippocampus.

Introduction: Direct current stimulation (DCS) can produce a lasting polarity-specific modulation of cortical excitability in the brain and its therapeutic potential is being investigated in several neurological diseases, including stroke, epilepsy, movement disorders and major depression. Some evidence suggests that the after-effects of DCS might be mediated by the interaction with molecular mechanisms of activity-dependent synaptic plasticity. Immediate early genes, such as c-fos and zif268, are rapidly induced following neuronal activation and may act as regulators of downstream target genes responsible for 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 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 on LTP induction at CA3-CA1 hippocampal synapses of rat brain slices. 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 both polarities of DCS produced a marked and consistent sub-region-specific increase in the expression of zif268 in the CA region of the hippocampus. Conclusions: Present data demonstrate that it is possible to modulate LTP induction by DCS and provide the rationale for the use of DCS in neurological diseases in order to promote adaptive and suppress maladaptive forms of brain plasticity.