Glycolysis and glycogenolysis are involved in memory processing in day-old chickens and, aside from the provision of energy for neuronal and astrocytic energy metabolism these pathways enable astrocytes to supply neurones with precursor for transmitter glutamate by glucose-based de novo synthesis. We have previously shown that memory processing for bead discrimination learning is dependent on glycolysis; however, the metabolic inhibitor used, iodoacetate, inhibits pyruvate formation from both glucose and glycogen. At specific time points after training transient reductions in brain glycogen content occur, mirrored by increases in glutamate/glutamine content. In the present study, we used intracerebral injection of a glycogen phosphorylase inhibitor, 1,4-dideoxy-1,4-imino-D-arabinitol (DAB), which does not affect glucose breakdown, to evaluate the role of glycogen metabolism in memory consolidation. Dose-dependent inhibition of learning occurred when DAB was administered at specific time periods in relation to training: (i) 5 min before training, (ii) around 30 min posttraining, and (iii) 55 min posttraining. After injection at either of the two earlier periods, memory disappeared after consolidation 30 min postlearning, and after injection 55 min after learning memory was absent at 70 min. The memory loss caused by early administration could be prevented after training by central injection of the glutamate precursor glutamine or the astrocyte-specific substrate acetate together with aspartate, substituting for pyruvate carboxylation. Thus, glycogenolysis is essential for learning in this paradigm and, aside from energy supply considerations, we suggest that an important role for glycogenolysis is to provide neurones with glutamine as the precursor for neuronal glutamate and GABA.

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Bead discrimination training in chicks sets in motion a tightly timed series of biochemical events, including glutamate release, increase in forebrain level of glutamate and utilization of glycogen and glucose. Inhibition of glycogen breakdown by the glycogen phosphorylase inhibitor 1,4-dideoxy-1,4-imino-D-arabinitol (DAB) around the time of training abolishes the increase in glutamate 5 min posttraining in the left hemisphere, in spite of uninhibited glucose metabolism. It also reduces the contents of glutamate, glutamine, and aspartate in the right hemisphere. Behavioral evidence supports the conclusion that glucose breakdown serves to provide energy, whereas glycogen acts as a substrate for glutamate, glutamine, and aspartate formation, requiring both pyruvate dehydrogenation to acetyl coenzyme A and pyruvate carboxylation in astrocytes. Inhibition of memory consolidation caused by DAB or 2-deoxyglucose (2-DG), an inhibitor of glucose phosphorylation without effect on glycogen metabolism, was challenged by intracerebral administration of acetate, aspartate, glutamine, lactate or glucose. DAB-mediated memory inhibition was successfully challenged by administration at 0 or 20 min posttraining of acetate (an astrocyte-specific acetyl CoA precursor) together with aspartate, substituting for pyruvate carboxylation, or of glutamine at 0-2.5 or 30 min posttraining. 2-DG-mediated memory impairment was not challenged by acetate with or without aspartate at 0 time but was challenged by acetate without aspartate at 20 min. Lactate, a substrate for both dehydrogenation and pyruvate carboxylation challenged both DAB and 2-DG. Doses of DAB and 2-DG which, on their own were subeffective, were not additive, further supporting the existence of one pathway using glucose and another using glycogen.