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Simultaneous assessment of cognitive function, circadian rhythm, and spontaneous activity in aging mice

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Abstract

Cognitive function declines substantially with age in both humans and animal models. In humans, this decline is associated with decreases in independence and quality of life. Although the methodology for analysis of cognitive function in human models is relatively well established, similar analyses in animal models have many technical issues (e.g., unintended experimenter bias, motivational issues, stress, and testing during the light phase of the light dark cycle) that limit interpretation of the results. These caveats, and others, potentially bias the interpretation of studies in rodents and prevent the application of current tests of learning and memory as part of an overall healthspan assessment in rodent models of aging. The goal of this study was to establish the methodology to assess cognitive function in aging animals that addresses many of these concerns. Here, we use a food reward-based discrimination procedure with minimal stress in C57Bl/6J male mice at 6, 21, and 27 months of age, followed by a reversal task to assess behavioral flexibility. Importantly, the procedures minimize issues related to between-experimenter confounds and are conducted during both the dark and light phases of the light dark cycle in a home-cage setting. During cognitive testing, we were able to assess multiple measures of spontaneous movement and diurnal activity in young and aged mice including, distance moved, velocity, and acceleration over a 90-h period. Both initial discrimination and reversal learning significantly decreased with age and, similar to rats and humans, not all old mice demonstrated impairments in learning with age. These results permitted classification of animals based on their cognitive status. Analysis of movement parameters indicated decreases in distance moved as well as velocity and acceleration with increasing age. Based on these data, we developed preliminary models indicating, as in humans, a close relationship exists between age-related movement parameters and cognitive ability. Our results provide a reliable method for assessing cognitive performance with minimal stress and simultaneously provide key information on movement and diurnal activity. These methods represent a novel approach to developing non-invasive healthspan measures in rodent models that allow standardization across laboratories.

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Acknowledgements

This work was supported by the funding sources: T32AG052363; NIH R01AG038747; R01NS056218; R01AG057424 to WES.

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Authors and Affiliations

  1. Reynolds Oklahoma Center on Aging, University of Oklahoma Health Sciences Center, 975 NE 10TH Street, SLY-BRC 1303, Oklahoma City, OK, 73104, USA

    Sreemathi Logan, Daniel Owen, Zoltan Ungvari, Julie Farley, Anna Csiszar, Arlan Richardson & William E. Sonntag

  2. Department of Biostatistics and Epidemiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA

    Sixia Chen & Wei-Jen Chen

  3. College of Pharmaceutical Sciences, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA

    Amanda Sharpe

  4. Sylics (Synaptologics BV), Amsterdam, The Netherlands

    Maarten Loos & Bastijn Koopmans

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  1. Sreemathi Logan
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  2. Daniel Owen
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  3. Sixia Chen
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  4. Wei-Jen Chen
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  5. Zoltan Ungvari
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  7. Anna Csiszar
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  9. Maarten Loos
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  10. Bastijn Koopmans
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  12. William E. Sonntag
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Correspondence to Sreemathi Logan.

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Logan, S., Owen, D., Chen, S. et al. Simultaneous assessment of cognitive function, circadian rhythm, and spontaneous activity in aging mice. GeroScience 40, 123–137 (2018). https://doi.org/10.1007/s11357-018-0019-x

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