Advances in the relationship between molecular genetics and behavioral neuroscience have led to the increased use of behavioral tasks that are sensitive to genotypic alterations. One task that is little used by behavioral neuroscientists is the measurement of rodent nesting behavior. Studies have shown that nesting behavior is dependent upon intact hippocampal function, as hippocampal lesions dramatically reduce the amount of daily nesting behavior seen in rats and gerbils. This relationship between nesting behavior and hippocampal lesioning led us to investigate nesting behavior in transgenic APP mouse models of Alzheimer's disease (AD).

AD-related pathology develops in the hippocampus of APPsw and PSAPP mouse models with age. We found that both APPsw and PSAPP mice demonstrated significantly attenuated nesting behavior when compared to their appropriate genetic controls, across a wide range of ages. This behavioral task is valuable because it possesses (1) high predictive validity and (2) high utility, as it is quite simple to collect data, and does not interfere with other behavioral procedures being conducted.

This work suggests that nesting behavior is an effective tool for phenotyping APP transgenic mice, and may be sensitive as a behavioral measure for determining potential therapeutic treatments for AD. Further studies will investigate changes in nesting behavior following therapeutic interventions, and examine the relationship between nesting behavior and hippocampal AD-related pathology.

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