Mitochondrial protein synthesis may be involved in long-term memory formation

The hypothesis that two qualitatively different stages of cerebral protein synthesis (PS) are required for the formation of long-term memory (LTM) for an active-avoidance task was investigated in rats. Cytoplasmic PS was inhibited with anisomycin (ANI—5.0 mg subcutaneously). When ANI was injected at 15 min pre- and 30 min posttraining, so that cerebral PS was inhibited by 90% for 2 hours starting just before training, LTM formation was prevented. When ANI was given after training, it was not effective. Mitochondrial PS was inhibited with chloramphenicol (CAP-1.5 mg intracisternally). Inhibition occured 40 min after the injection. CAP interfered with LTM formation only when injected between 15 and 55 min after training. From these data it was concluded that two stages of PS are required for the formation of LTM. The first one takes place in the cytoplasm, starts with the commencement of training and is independent of newly synthesized mRNA. The second stage takes place in mitochondria starting approximately 25 min after training and is dependent upon newly formed mRNA.