Hippocampal Arc Induces Decay of Object Recognition Memory in Male Mice

Abstract

Activity-regulated cytoskeleton-associated (Arc) gene is one of the effector neuronal immediate early genes (IEG) that is rapidly upregulated after neuronal activation and is involved in synaptic long-term potentiation and depression. In recent years, it has been implicated in several cognitive disorders, viz. Angelman syndrome, Alzheimer's disease, fragile-X syndrome, etc. It undergoes quick transcription and highly regulated translation after exposure to a novel environment. Previous studies have shown that the presence of Arc mRNA primes mGluR-dependent long-term depression (LTD) in previously activated synapses upon re-exposure to the same environment. These studies suggest that the memory could be affected by the availability of Arc at the re-exposure time. Therefore, to confirm this, we investigated the changes in the temporal order memory and object recognition memory after the re-exposure to an environment in male mice. We studied the involvement of Arc in these changes by inhibiting Arc protein expression via stereotaxic infusions of Arc antisense oligodeoxynucleotides in the hippocampus of mice. We found that both temporal order and object recognition memories are dependent on the inter-familiarization phase interval. Strikingly, we also found that Arc accelerated the memory decay of an object when mice were re-exposed to the environment without that object.

Keywords: arc; hippocampus; memory; novel experience; object recognition; temporal order.