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Evoked granule cell field potentials, and levels of tissue metabolites, in superfused guinea-pig hippocampal slices have been studied in the presence of low glucose and an alternative glycolytic substrate (D-fructose). The effects of glucose analogues (5-thio-D-glucose, 2-deoxy-D-glucose or 3-O-methyl-D-glucose) in the presence of glucose were also tested. Concentrations of glucose or fructose in excess of 2 mM and 10 mM respectively were required to maintain normal evoked activity. 5-Thioglucose (15 mM) in the presence of 5 mM-glucose decreased the amplitude of the population spike by 60% with little effect on population excitatory post-synaptic potential (e.p.s.p.). Tissue levels of phosphocreatine and ATP were essentially unchanged under all conditions tested, with the exception of 10 mM-fructose. The decrease in rates of lactate efflux from superfused tissue during and after superfusion with 3-O-methylglucose, 2-deoxyglucose or 5-thioglucose was found to be positively correlated with the extent of attenuation of field potentials. Analysis of the relationship between population spike amplitude and rates of rise of e.p.s.p., under conditions where field potentials were attenuated, showed that the population spike was always more sensitive to metabolic perturbation than was the e.p.s.p., thus indicating an effect on cell excitability. It is suggested that some aspect of non-oxidative glucose metabolism is important in maintaining this granule cell excitability.

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