Investigating the effects of intrahippocampal glucose administration on spatial working memory in rats

Lecture Center 6

Insulin is a peptide hormone released by pancreatic cells that is known to regulate absorption of glucose into peripheral tissue. Insulin is also known to regulate glucose metabolism through the activation of the phosphoinositide 3-kinase (PI3K) signaling cascade and translocation of glucose transporter 4 (GLUT4) to the cell surface. This canonical insulin signaling pathway is similar in both the periphery and the central nervous system (CNS). In vivo microdialysis studies have shown depletion of hippocampal extracellular fluid (ECF) glucose concentration during a cognitively-demanding task, indicating that the hippocampus depends on glucose metabolism for proper function. In order to maintain proper function, insulin-responsive hippocampal neurons and glia require glucose metabolism; an energy-yielding process that provides glucose. We hypothesized that insulin blockage attenuates glucose-induced hippocampal enhancement via disruption of the insulin signaling pathway. The present study aimed to investigate insulin’s role as a mediator of the enhancement of spatial working memory by exogenous glucose in vivo. Unexpectedly, unilateral intrahippocampal administration of supraphysiological glucose in a novel, larger microinjection volume significantly impaired spatial working memory. Our data suggest the insulin signaling pathway may work through alternative substrates, such as insulin-like growth factors I or II. Standard administration of supraphysiological glucose resulted in no significant effect on hippocampal function, suggesting that unilateral administration may be insufficient in affecting hippocampal function. Our results also suggest glucose-induced improvement of hippocampal function may work in a dose-dependent manner in the hippocampus. These unexpected findings contribute to the knowledge of glucose-induced hippocampal enhancement and its relation to proper insulin signaling.