Fluctuations in brain glucose concentration during behavioral testing: dissociations between brain areas and between brain and blood

Traditional beliefs about two aspects of glucose regulation in the brain have been challenged by recent findings. First, the absolute level of glucose in the brain's extracellular fluid appears to be lower than previously thought. Second, the level of glucose in brain extracellular fluid is less stable than previously believed. In vivo brain microdialysis was used, according to the method of zero net flux, to determine the basal concentration of glucose in the extracellular fluid of the striatum in awake, freely moving rats for comparison with recent hippocampal measurements. In addition, extracellular glucose levels in both the hippocampus and the striatum were measured before, during, and after behavioral testing in a hippocampus-dependent spontaneous alternation task. In the striatum, the resting extracellular glucose level was 0.71 mM, approximately 70% of the concentration measured previously in the hippocampus. Consistent with past findings, the hippocampal extracellular glucose level decreased by up to 30 +/- 4% during testing; no decrease, and in fact a small increase (9 +/- 3%), was seen in the striatum. Blood glucose measurements obtained during the same testing procedure and following administration of systemic glucose at a dose known to enhance memory in this task revealed a dissociation in glucose level fluctuations between the blood and both striatal and hippocampal extracellular fluid. These findings suggest, first, that glucose is compartmentalized within the brain and, second, that one mechanism by which administration of glucose enhances memory performance is via provision of increased glucose supply from the blood specifically to those brain areas involved in mediating that performance.