Consolidation of spatial memory in the rat: Findings using zeta-inhibitory peptide

Whether or not spatial memories reorganize in the rodent brain is an unanswered question that carries the importance of whether the rodent provides a suitable animal model of human retrograde amnesia. The finding of equally impaired recent and remote spatial memory could reflect the continued importance of the hippocampus for spatial memory or a performance deficit (for example, hippocampal lesions may impair the rat's ability to use distal spatial cues to navigate to a specific point in space). In the current study, we tested recent and remote spatial memory in rats following hippocampal ZIP (zeta-pseudosubstrate inhibitory peptide) infusion to inhibit PKMzeta. Hippocampal ZIP infusion has previously been shown to impair spatial and nonspatial memory soon after learning, presumably by reversing late-phase long-term potentiation, allowing us to disrupt memory without damaging hippocampal tissue. We used a stereotaxic approach for infusing ZIP throughout the dorsal, intermediate, and ventral hippocampus following spatial memory training. Although rats showed intact memory retrieval on the standard Morris watermaze task and trace fear conditioning, rats infused with ZIP 24h after training on the annular watermaze task exhibited impaired spatial memory compared to control rats (those infused with aCSF) and performed no different than chance. In contrast, rats infused with ZIP 1month after training performed similar to control rats and both groups performed above chance. Additionally, the ability to form new memories after ZIP infusions remained intact. Thus, ZIP infusions into the hippocampus after learning impaired retrieval of recently formed spatial memories while sparing remote spatial memories.