DEPLETION OF GLUCOSE CAUSES PRESYNAPTIC INHIBITION OF NEURONAL TRANSMISSION IN THE RAT DORSOLATERAL SEPTAL NUCLEUS

The role of glucose in synaptic transmission was examined in the rat d orsolateral septal nucleus (DLSN) with single-microelectrode voltage-c lamp and slice-patch techniques. Removal of glucose from the oxygenate d Krebs solution caused an outward current associated with an increase d membrane conductance. The current-voltage relationship (I-V curve) s howed that the hypoglycemia-induced outward current was reversed in po larity at the equilibrium potential for K+. Exposure of DLSN neurons t o the glucose-free solution for 5-20 min depressed the excitatory post synaptic current (EPSC), the inhibitory postsynaptic current (IPSC), a nd the late hyperpolarizing current (LHC). Replacement of glucose with 8-deoxy-D-glucose (2DG), an antimetabolic substrate, mimicked the dep rivation of glucose. Mannoheptulose (10 mM) and dinitrophenol, inhibit ors of glucose metabolism, also depressed the PSCs, even in the presen ce of 10 mM glucose. Glucose-free perfusion did not significantly depr ess the glutamate-induced inward current, indicating that the inhibiti on of the EPSC by the glucose-free perfusion was presynaptic. gamma-am inobutyric acid (GABA)-induced outward currents were depressed by the glucose-free solution. Intracellular dialysis of DLSN neurons with a p atch-pipette solution containing 5 mM ATP attenuated the hypoglycemia- induced outward current. Glucose-free superfusion consistently inhibit ed the IPSC and the LHC without changing the GABA-induced outward curr ent in ATP-treated DLSN neurons. It is suggested that glucose metaboli sm directly regulates the release of both excitatory amino acids and G ABA from the presynaptic nerve terminals. (C) 1996 Wiley-Liss, Inc.