Differential requirements of hippocampal de novo protein and mRNA synthesis in two long-term spatial memory tests: Spontaneous place recognition and delay-interposed radial maze performance in rats.

Hippocampal de novo mRNA and protein synthesis has been suggested to be critical for long-term spatial memory. However, its requirement in each memory process (i.e. encoding, consolidation and retrieval) and the differences in the roles of de novo mRNA and protein synthesis in different situations where spatial memory is tested have not been thoroughly investigated. To address these questions, we examined the effects of hippocampal administration of the protein synthesis inhibitors, anisomycin (ANI) and emetine (EME), as well as that of an mRNA synthesis inhibitor, 5,6-dichlorobenzimidazole 1-β-D-ribofuranoside (DRB), on rat performance in two long-term spatial memory tests. In a spontaneous place recognition test with a 6 h delay, ANI, administered either before or immediately after the sample phase, but not before the test phase, eliminated the exploratory preference for the object in a novel place. This amnesic effect was replicated by both EME and DRB. In a 6 h delay-interposed radial maze task, however, administering ANI before the first-half and before the second-half, but not immediately or 2 h after the first-half, impaired performance in the second-half. This disruptive effect of ANI was successfully replicated by EME. However, DRB administered before the first-half performance did not impair the second-half performance, while it did impair it if injected before the second-half. None of these drugs caused amnesic effects during the short (5 min)/non-delayed conditions in either tests. These results suggest that 1) hippocampal protein synthesis is required for the consolidation of spatial memory, while mRNA synthesis is not necessarily required, and 2) hippocampal mRNA and protein synthesis requirement for spatial memory retrieval depends on the types of memory tested, probably because their demands are different.