INVOLVEMENT OF NITRIC-OXIDE IN LOW GLUCOSE-MEDIATED INHIBITION OF HIPPOCAMPAL LONG-TERM POTENTIATION

Hypoglycemia is associated with deficits in learning and memory, yet t here is little information about how changes in extracellular glucose alter processes involved in memory. To address these issues, we examin ed the effects of low glucose on long-term potentiation (LTP) in the C A1 region of rat hippocampal slices. When slices were exposed to 2-3.3 mM glucose for 5-30 min before tetanic stimulation, baseline synaptic responses were unaltered, but LTP could not be induced. However, expo sure to 2 mM glucose immediately following a tetanus failed to inhibit LTP. An inhibitor of N-methyl-D-aspartate (NMDA) receptors prevented the inhibition of LTP by 3.3 mM glucose, but was ineffective against 2 mM glucose. Similarly, nitric oxide synthase (NOS) inhibitors prevent ed LTP inhibition by 3.3 mM but not by 2 mM glucose. These results sug gest that untimely activation of NMDA receptors and release of NO cont ributes to low glucose-mediated LTP inhibition, but that different mec hanisms may be responsible for LTP inhibition depending on the severit y of hypoglycemia. (C) 1997 Wiley-Liss, Inc.