Abstracts

Rationale: 30 % of seizure patients suffered from drug-resistant epilepsy. Clinical application of TMS, tDCS and electric field stimulation provide non-invasive approaches for the treatment. Field stimulation could modulate synaptic plasticity as well as influence epileptiform activities in various brain regions. However, seldom research focus on the field effect on synaptic transmission within thalamocortical system. The medial dorsal (MD) thalamic nucleus is heavily connected to anterior cingulate cortex (ACC) and medial prefrontal cortex(mPFC) and could regulate seizure activities in cortical regions. Seizures generated in mPFC and ACC are often drug-resistant. Therefore, the current study is aimed to investigate the effect of DC field stimulation on the changes of thalamocingulate synaptic plasticity and seizure. Methods: B6 mice were used. Brain slice preserve the pathway between MD and ACC was used in this study. The field potentials were recorded with multielectrode array. Data were acquired by the PC based data software MC_Rack at a sampling rate of 10 kHz and analyzed with MATLAB 7.5. Uniform electric fields were generated by passing constant current between two parallel AgCl-coated silver wires. Currents were generated by a stimulator under the control of a pulse generator.Results: Application of anodal DC could potentiate the synaptic transmission in the MD-ACC pathway. The potentiation effect could last at least 60 minutes. The potentiation effect was mediated by the volume changes of extracellular space, which will in turn increase the concentration of neurotransmitter. The potentiation was prevented by the application of furosemide which was used to stabilize the extracellular space. The effect of DC field stimulation on synaptic potentiation was also blocked by the application of APV, the NMDA receptor antagonist. Drug resistant seizure was induced by perfusion brain slice with 4-aminopyridine (250 M) and bicuculline (5 M), application of anodal DC enhanced seizure activities while cathodal DC suppressed them. Furosemide abolished the effect of DC field on seizure-like activities, which indicated that DC field also influence the seizure-like activities by the modulation of extracellular space. Conclusions: DC mediated potentiation is caused by increasing concentration of neurotransmitter because application of furosemide and APV could prevent potentiation. Cathodal DC could suppress spontaneous and thalamic-evoked seizure-like activities, while anodal DC application has opposite effects. Field effect on seizure-like activities is caused by the alterations of extracellular potassium concentration which is mediated by NKCC cotransporter.