The research described in this proposal is designed to investigate the role(s) of glucose metabolism, particularly mitochondrial glucose metabolism in memory formation and cognitive function. It has been found that D-glucose, administered peripherally or centrally in conjunction with training can facilitate memory and can reverse the effects of memory impairing drugs. The proposed experiments are designed to reconcile the behavioral phenomenon with its underlying biochemistry, and to this effect will examine the metabolism of glucose in specific cerebral regions in the rat in conjunction with behavioral tasks known to be sensitive to modulation by glucose. Of particular interest is neuronal and glial mitochondrial function and the relative contributions of mitochondrial glucose metabolism to energy production and to the provision of substrates for neurotransmitter biosynthesis. By selective blocking specific metabolic pathways coupled with behavioral testing and/or assaying the activity of key enzymes involved in glucose metabolism, it should be possible to trace glucose flux in the anatomical regions involved in specific memory-dependent tasks. The studies described herein should also provide information on the response of neural tissue to conditions of hypoglycemia, ischemia and other pathological states.
