Abstracts

Rationale: The efficacy of electrical stimulation for neurological disorders such as epilepsy may be influenced by the strength and density of the connections between the stimulating region and pathogenic focuses. We investigated whether the number of stimulation sites affected the network distribution of long-term depression (LTD) of synaptic efficacy, and whether the network distribution affected the anticonvulsant efficacy of LTD induced in a spontaneously epileptic in vitro preparation. Methods: Long-term (3-4 hour) recordings of spontaneous multiple init activity (MUA), population field activity and evoked field excitatory postsynaptic potentials were performed in the intact hippocampus in vitro from male Sprague Dawley rats at postnatal day 4 (P4) to P7. Spontaneous epileptiform discharges were elicited by transient perfusion of kainate and gabazine. Results: Recurrent ictal and interictal epileptiform discharges were characterized by multifocal onset and three-dimensional propagation. Low-frequency electrical stimulus trains (900 stimuli, 1 Hz) produced 20-30 min depression by 22 % (n = 3) as measured by the amplitude of the evoked field EPSP. The 1 Hz stimulus trains also reduced the amplitude and duration of spontaneously occurring epileptiform discharges in proximal hippocampal networks, but were less effective or completely ineffective at reducing the amplitude and frequency of epileptiform activity at sites distal to the stimulating electrode. Simultaneous stimulation of two widely separated sites in the septal and temporal areas increased the degree of LTD induced in both areas. LTD induced by 2 stimulation sites was associated with significantly reduced interictal and ictal-like discharge probability when compared to LTD induced by stimulus trains at a single site, and was more effective at depressing the amplitude and duration of spontaneous epileptiform discharges.Conclusions: Our study demonstrates increased efficacy of multifocal vs unifocal stimulation for both the distribution of LTD and the consequent control of multifocal discharges in the epileptic networks.