Previous results from our laboratory have shown pharmacological activation of nicotinic acetylcholine receptors (nAChRs) to produce a sustained pro-epileptogenic action within the hippocampal slice (Roshan-Milani et al., 2003). The aim of the present study was to identify possible excitatory or inhibitory circuits through which activation of nAChRs produce their pro-epileptogenic effects.Hippocampal slices (400µm thick) prepared ex vivo from male Wistar rats (2-3 weeks), killed by cervical dislocation and decapitation, were transferred to a submerged-type recording chamber. Extracellular field recordings were made in the Stratum pyramidale of the CA1 and CA3 regions to investigate evoked synaptic responses. For subsequent experiments investigating spontaneous and miniature synaptic events, hippocampal slices (250µm thick) were prepared from Wistar rats (16-21 days) terminally anaesthetized with pentobarbitone (1000mg/kg i.p). Slices were viewed under IR-DIC optics and whole-cell patch clamp recordings made from visually identified interneurones and pyramidal cells. Initial experiments investigated the action of nAChRs on basal glutamatergic transmission. Bath application of the selective nAChR agonist dimethylphenylpiperanzinium (DMPP, 30µM) resulted in a sustained and reversible enhancement of glutamate afferent evoked field EPSP slope in the CA3 region of the hippocampus by 29.8±6.19% (mean±SEM; p=0.0078, wilcoxon matched pairs test, n=8) but not in the CA1 (2.84±10.04, p=0.625, wilcoxon matched pairs test, n=5). This data suggests that glutamate transmission was enhanced by nAChR activation in the CA3 region of the hippocampus but not the CA1.In further studies to investigate nAChR regulation of GABAergic transmission, whole-cell patch clamp recordings were carried out in the CA1 region. Application of DMPP (30µM) increased the frequency of spontaneous IPSCs recorded in CA1 interneurones from 7.5±1.94 to 13.1±2.8Hz (mean±SEM; p=0.040, paired t test, n=7). Overall there was no significant change in IPSC amplitude (20.42±2.47 to 23.41±3.04 pA, p=0.0836, paired t test, n=7). Subsequent experiments carried out in the presence of TTX allowed recording of miniature IPSCs. DMPP (30µM) increased frequency of mIPSCs recorded in CA1 interneurones from 0.53±0.091 to 1.02±0.125Hz (mean±SEM; p=0.01, paired t test, n=4) but had no effect on the frequency of mIPSCs recorded in CA1 pyramidal cells (3.32±2.54 to 3.16±2.28Hz, p=0.578, paired t test, n=4).In conclusion, activation of nAChRs may produce pro-epileptogenic actions through regulating both glutamatergic and GABAergic circuits, resulting in both direct excitatory and disinhibitory actions respectively.