In the present study, acute responsive stimulation was delivered to one subregion of the hippocampus – the subiculum – in kainic acid (KA) treated rats. The subiculum is the major output structure in the hippocampal network (Witter and Groenewegen 1990; O’Mara et al. 2001), receiving fibers mainly from the CA1 field and projecting to the entorhinal cortex (EC), other cortical and subcortical structures (O’Mara 2005). Spontaneous Inhibitors,research,lifescience,medical rhythmic activity has been found in the isolated subiculum in human slices (Cohen et al. 2002; Wozny et al. 2003).

It was also found that the subiculum was hyperexcitable when activated by CA1 or EC inputs in brain slices of pilocarpine treated rats (de Guzman et al. 2006). Taken together, the subiculum is rather prone to synchronous activities and has never been studied in the effects of responsive stimulation or scheduled stimulation to control seizures. The aim of the study was to investigate the effects of responsive subicular HFS on temporal lobe seizures. A semi-acute temporal lobe Inhibitors,research,lifescience,medical seizure model was

used: repeated injections of low dose KA intrahippocampally. With this seizure model not only different severities of seizures can be obtained Inhibitors,research,lifescience,medical but also a large definitely number of seizures within a limited period. The presence of multiple focal and generalized seizures within a limited time frame provide us with multiple possibilities to intervene with responsive stimulation. The effects of responsive subicular stimulation were compared with a sham group. It is hypothesized that acute responsive HFS of the subiculum would interrupt seizures or reduce the rate of seizures and interictal Inhibitors,research,lifescience,medical spikes. Materials and Methods Animals Male Wistar rats (n = 20), weighing 451 ± 47 g, were used (bred

at the Biological Psychology Department, Radboud University Nijmegen). The rats were housed under controlled temperature (20°C, relative humidity 50–70%) and light conditions (12 h light/dark cycle with lights on at 8:00 A.M.), with ad libitum access to food and water. The local medical-ethical committee of the Inhibitors,research,lifescience,medical Radboud University Nijmegen (RU-DEC) approved all procedures on animal experimentation Brefeldin_A in this study. Efforts were taken to alleviate discomfort and number of animals in the study as much as possible. Simultaneous electrode-guide combinations Simultaneous electrode-guide combinations (C315G-MS303/2; Plastics One, Roanoke, VA) comprised of a 26-gauge guide cannula and two insulated stainless steel wires glued to the guide cannula. This electrode-guide complex enables us to deliver KA into the injection site, record and stimulate very near the injection site. A dummy was used to close the guide cannula. The tips of bipolar electrodes were 1 mm shorter than the tip of cannula. Surgery The rats were anesthetized with isoflurane inhalation and fixed in a stereotaxic frame.