Cycloheximide-induced inhibition of protein synthesis in hippocampal pyramidal neurons is time-dependent: differences between CA1 and CA3 areas.

Cycloheximide (CHI), an inhibitor of protein synthesis, is widely used for studying the mechanisms of consolidation of long-term memory (LTM). High concentrations of CHI inhibit the protein synthesis in brain homogenates by more than 80% and impair LTM consolidation. For understanding the mechanisms of consolidation, it is important to know how protein synthesis inhibitors affect hippocampal neurons. However, the effect of CHI on protein synthesis in CA1 and CA3 hippocampal pyramidal neurons is still poorly understood. In the present work, the state of ribosomes in CA1 and CA3 pyramidal neurons from the dorsal hippocampus of Wistar rats 1, 2, 4, and 72 h after the introcerebroventricular (i.c.v.) injection of a high concentration of CHI was determined using the fluorescent dye acridine orange. We showed that CHI induces great differences in the dynamics of the intensity of protein synthesis in CA1 and CA3 pyramidal neurons. The suppression of the intensity of protein synthesis in CA1 pyramidal neurons 1h after the injection of CHI was more than threefold stronger than in CA3, and by 4h, it was most pronounced in CA3 neurons. We suggest that the protein synthesis in CA1 pyramidal neurons contributes significantly to the synaptic consolidation of declarative memory in the first critical period.