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.
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