Decreases in rat extracellular hippocampal glucose concentration associated with cognitive demand during a spatial task

Abstract

Using in vivo microdialysis, we measured hippocampal extracellular glucose concentrations in rats while they performed spontaneous alternation tests of spatial working memory in one of two mazes. Extracellular glucose levels in the hippocampus decreased by 32% below baseline during the test period on the more complex maze, but by a maximum of 11% on the less complex maze. Comparable decreases were not observed in samples taken from rats tested on the more complex maze but with probes located near but outside of the hippocampus. Systemic glucose fully blocked any decrease in extracellular glucose and enhanced alternation on the more complex maze. These findings suggest that cognitive activity can deplete extracellular glucose in the hippocampus and that exogenous glucose administration reverses the depletion while enhancing task performance.

Figure 1

Mean extracellular hippocampal glucose concentrations during +-maze testing, expressed as a percentage of baseline concentration. Samples 1–4 are pretesting baseline; samples 5–8 (shaded area) are during testing for those groups tested; samples 9–12 are posttesting. All rats were handled between samples 4 and 5 and between samples 8 and 9, whether or not being tested on the maze. □, Control group (no treatment, no testing); ⋄, +-maze group (no treatment); ■, +-maze saline group (1.0 ml of sterile saline, i.p., 30 min pretesting); ♦, +-maze glucose group (1.0 ml of 250 mg/kg, i.p., 30 min pretesting); ▵, glucose group (no testing, glucose as in +-maze glucose group). Error bars = SEM.

Figure 2

Mean 4/5 alternation performance on +-maze, expressed as a percentage of possible alternations. Error bars = SEM.

Figure 3

Mean extracellular hippocampal glucose concentrations (as in Fig. 1), but during Y-maze testing. ⊠, Y-maze group (no treatment); ●, Y-maze glucose group (1.0 ml of 250 mg/kg, i.p., 30 min pretesting); ⋄, +-maze group (no treatment), repeated from Fig. 1 for ease of comparison. Error bars = SEM. ∗, Group difference between Y-maze- and +-maze-tested groups, P < 0.05.

Figure 4

Mean 3/3 alternation performance on Y-maze, expressed as a percentage of possible alternations. Error bars = SEM.

Figure 5

Mean extracellular hippocampal glucose concentration (details as in Fig. 1). ▴, +-Maze group (no treatment) animals with misplaced cannulae; ⋄, +-maze (no treatment) animals with cannulae in hippocampus, repeated from Fig. 1.