Hippocampal Infusion of Zeta Inhibitory Peptide Impairs Recent, but Not Remote, Recognition Memory in Rats.

Jena B Hales,Robert E Clark,Nicola J Broadbent,Amber C Ocampo

doi:10.1155/2015/847136

Abstract

Spatial memory in rodents can be erased following the infusion of zeta inhibitory peptide (ZIP) into the dorsal hippocampus via indwelling guide cannulas. It is believed that ZIP impairs spatial memory by reversing established late-phase long-term potentiation (LTP). However, it is unclear whether other forms of hippocampus-dependent memory, such as recognition memory, are also supported by hippocampal LTP. In the current study, we tested recognition memory in rats following hippocampal ZIP infusion. In order to combat the limited targeting of infusions via cannula, we implemented a stereotaxic approach for infusing ZIP throughout the dorsal, intermediate, and ventral hippocampus. Rats infused with ZIP 3–7 days after training on the novel object recognition task exhibited impaired object recognition memory compared to control rats (those infused with aCSF). In contrast, rats infused with ZIP 1 month after training performed similar to control rats. The ability to form new memories after ZIP infusions remained intact. We suggest that enhanced recognition memory for recent events is supported by hippocampal LTP, which can be reversed by hippocampal ZIP infusion.

Highlights

Several reports have demonstrated that spatial memory can be erased by infusing zeta inhibitory peptide (ZIP), a cellpermeable synthetic peptide, into the dorsal hippocampus [1,2,3]
On a retention test approximately 1 week after surgery, the recent ZIP group exhibited impaired object recognition memory compared to the aCSF and unoperated control groups
The remote ZIP group performed similar to the remote aCSF group (Figures 2, 3(a), and 3(b))

Summary

Introduction

Several reports have demonstrated that spatial memory can be erased by infusing zeta inhibitory peptide (ZIP), a cellpermeable synthetic peptide, into the dorsal hippocampus [1,2,3]. LTP is a function of enhanced AMPA receptormediated transmission at potentiated synapses, and ZIP is thought to interrupt the intercellular signaling pathways that traffic and maintain AMPA receptors at the postsynaptic density [4] Such findings are important because they add to a substantial literature showing that the hippocampus is critical for spatial memory. In the Hardt et al [3] study, as well as in all other studies that have infused ZIP into the hippocampus, only the dorsal aspect of the hippocampus was targeted This is because the standard method is to implant bilateral indwelling guide cannulas into the hippocampus so that ZIP can be infused after the training episode. Because prior work has demonstrated that recognition memory starts out as being hippocampus-dependent but becomes hippocampusindependent during the weeks after learning [16], we examined how reversing LTP with ZIP infusions affected both recent memory (3–7 days old) and remote memory (1 month old)

Methods

Results

Discussion