Cited by 110Animal Behavior and Welfare StudiesNeuroscience and Neuropharmacology ResearchMemory and Neural Mechanisms

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Measuring Behavior in the Home Cage: Study Design, Applications, Challenges, and Perspectives

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Grieco, Fabrizio, Bernstein, Briana J., Biemans, Barbara, Bikovski, Lior, Burnett, C. Joseph, Cushman, Jesse D., van Dam, Elsbeth A., Fry, Sydney A., Richmond-Hacham, Bar, Homberg, Judith R., Kas, Martien J. H., Kessels, Helmut W., Koopmans, Bastijn, Krashes, Michael J., Krishnan, Vaishnav, Logan, Sreemathi, Loos, Maarten, McCann, Katharine E., Parduzi, Qendresa, Pick, Chaim G., Prevot, Thomas D., Riedel, Gernot, Robinson, Lianne, Sadighi, Mina, Smit, August B., Sonntag, William, Roelofs, Reinko F., Tegelenbosch, Ruud A.J., Noldus, Lucas P.J.J.·2021·Frontiers in Behavioral Neuroscience

DOI 10.3389/fnbeh.2021.735387PMC PMC8498589

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Abstract

The reproducibility crisis (or replication crisis) in biomedical research is a particularly existential and under-addressed issue in the field of behavioral neuroscience, where, in spite of efforts to standardize testing and assay protocols, several known and unknown sources of confounding environmental factors add to variance. Human interference is a major contributor to variability both within and across laboratories, as well as novelty-induced anxiety. Attempts to reduce human interference and to measure more "natural" behaviors in subjects has led to the development of automated home-cage monitoring systems. These systems enable prolonged and longitudinal recordings, and provide large continuous measures of spontaneous behavior that can be analyzed across multiple time scales. In this review, a diverse team of neuroscientists and product developers share their experiences using such an automated monitoring system that combines Noldus PhenoTyper® home-cages and the video-based tracking software, EthoVision® XT, to extract digital biomarkers of motor, emotional, social and cognitive behavior. After presenting our working definition of a “home-cage”, we compare home-cage testing with more conventional out-of-cage tests (e.g., the open field) and outline the various advantages of the former, including opportunities for within-subject analyses and assessments of circadian and ultradian activity. Next, we address technical issues pertaining to the acquisition of behavioral data, such as the fine-tuning of the tracking software and the potential for integration with biotelemetry and optogenetics. Finally, we provide guidance on which behavioral measures to emphasize, how to filter, segment, and analyze behavior, and how to use analysis scripts. We summarize how the PhenoTyper has applications to study neuropharmacology as well as animal models of neurodegenerative and neuropsychiatric illness. Looking forward, we examine current challenges and the impact of new developments. Examples include the automated recognition of specific behaviors, unambiguous tracking of individuals in a social context, the development of more animal-centered measures of behavior and ways of dealing with large datasets. Together, we advocate that by embracing standardized home-cage monitoring platforms like the PhenoTyper, we are poised to directly assess issues pertaining to reproducibility, and more importantly, measure features of rodent behavior under more ethologically relevant scenarios.

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Authors: Grieco, F., Bernstein, B. J., Biemans, B., Bikovski, L., Burnett, C. J., Cushman, J. D., van Dam, E. A., Fry, S. A., Richmond-Hacham, B., Homberg, J. R., Kas, M. J. H., Kessels, H. W., Koopmans, B., Krashes, M. J., Krishnan, V., Logan, S., Loos, M., McCann, K. E., Parduzi, Q., Pick, C. G., Prevot, T. D., Riedel, G., Robinson, L., Sadighi, M., Smit, A. B., Sonntag, W., Roelofs, R. F., Tegelenbosch, R. A. J., & Noldus, L. P. J. J.
Affiliations: Noldus Information Technology (NL)
National Institutes of Health (US)
F. Hoffmann-La Roche AG (CH)
Tel Aviv University (IL)
Icahn School of Medicine at Mount Sinai (US)
Radboud University Medical Center (NL)
University of Groningen (NL)
University of Amsterdam (NL)
Sylics (Netherlands) (NL)
Baylor College of Medicine (US)
University of Oklahoma Health Sciences Center (US)
University of Aberdeen (GB)
Vrije Universiteit Amsterdam (NL)
Radboud University Nijmegen (NL)
Corresponding author: Noldus, Lucas P.J.J.
ORCID: Grieco, Fabrizio
Bernstein, Briana J.
Biemans, Barbara
Bikovski, Lior
Burnett, C. Joseph
Cushman, Jesse D.
van Dam, Elsbeth A.
Fry, Sydney A.
Richmond-Hacham, Bar
Homberg, Judith R.
Kas, Martien J. H.
Kessels, Helmut W.
Koopmans, Bastijn
Krashes, Michael J.
Krishnan, Vaishnav
Logan, Sreemathi
Loos, Maarten
McCann, Katharine E.
Parduzi, Qendresa
Pick, Chaim G.
Riedel, Gernot
Robinson, Lianne
Smit, August B.
Sonntag, William
Noldus, Lucas P.J.J.
Venue: Frontiers in Behavioral Neuroscience
Publisher: Frontiers Media SA
Published: 2021-09-24
Volume: 15
Pages: 735387-735387
ISSN: 1662-5153 (ISSN-L)
DOI: 10.3389/fnbeh.2021.735387
PMC: PMC8498589
OpenAlex: W3200442339
Cited by: 109
References: 255
Citations by year: 2026: 21 · 2025: 36 · 2024: 16 · 2023: 25 · 2022: 11
FWCI: 14.84
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (vor)
Locations: Frontiers in Behavioral Neuroscience (publishedVersion, cc-by)
Europe PMC (PubMed Central) (publishedVersion, other-oa)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
VU Research Portal (publishedVersion, other-oa)
UvA-DARE (University of Amsterdam) (submittedVersion, other-oa)
Radboud Repository (Radboud University) (submittedVersion, other-oa)
Aberdeen University Research Archive (Aberdeen University) (submittedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, cc-by)
Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
Funders: National Institutes of Health
National Institute on Aging (R00AG056662)
National Institute of General Medical Sciences (P20GM125528)
Topics: Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Behavior and Welfare Studies
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
Keywords: home cage monitoring, automated video tracking, digital biomarkers, rodent behavior, replication crisis, human disturbance, biotelemetry, optogenetics, behavioral segmentation, neuropharmacology, animal models of neurodegeneration, within-subject analysis

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Measuring Behavior in the Home Cage: Study Design, Applications, Challenges, and Perspectives

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