Using hippocampal slices from guinea pigs, we investigated the effect of different concentrations of glucose and replacement of glucose with mannose, fructose and lactate on neural activity. As an index of neural activity, the population spikes (PS) were recorded in the granule cell layer of the dentate gyrus (DG) and the pyramidal cell layer of the CA3 area in the hippocampal slices. Lowering the concentration of glucose from 10 mM to 5, 3, 2, 1 and 0 mM caused a reduction in the PS amplitude. There were differences in the decay times of the PS evoked in these two regions. PS evoked in CA3 region decayed faster even at a concentration of 3 mM glucose at which PS in granule cell layer was well maintained. The decay time of the PS in the CA3 region in the presence of glucose up to a concentration of 3 mM was shorter than that evoked in the DG, After the replacement of glucose with mannose, fructose or lactate, the PS disappeared within 35 min and there were no significant differences between the decay times in the two regions of slices incubated in the same medium. ATP, creatine phosphate (CrP) and lactate levels in each slice were determined. To investigate whether mannose and fructose could be metabolized or not in the tissue slice, anaerobic production of lactate from glucose, mannose and fructose were measured during oxygen and glucose deprivation, Under anaerobic conditions for 60 min, the levels of high-energy phosphates decreased to 50% of the initial level and lactate was produced from glucose, mannose or fructose. However, there were significant differences in the rate of lactate production between the DG and CA3 areas during application of 3 mM glucose, 10 mM mannose and 10 mM fructose. These results indicate that mannose, fructose and lactate can be metabolized and are available for maintaining the levels of high-energy phosphates but not for neural activity in the tissue slices and that the presence of glucose is indispensable for the maintenance of neural activity. (C) 1998 Elsevier Science B.V.