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

Grieco, Fabrizio; Bernstein, Briana J.; Biemans, Barbara; Bikovski, Lior; Burnett, C. Joseph; Cushman, Jesse D.; Dam, Elsbeth A. van; Fry, Sydney A.; Richmond-Hacham, Bar; Homberg, Judith R.; Kas, Martien; 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, Mehrnoosh; Smit, August B.; Sonntag, William E.; Roelofs, Reinko F.; Tegelenbosch, Ruud A.J.; Noldus, L.P.J.J.

doi:10.3389/fnbeh.2021.735387

Cited by 54 publications

(55 citation statements)

References 235 publications

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“…In this research, we used an automated HCM approach with multiple advantages to assess subtle anxiety-like behaviors in LIB-exposed mice ( Table 1 ). 24 , 37 , 38 With the HCM system, animal behaviors under both natural and challenged conditions can be assessed for distinct spontaneous and affective behaviors. 19 , 25–27 Automated, continuous assessments for extended periods in multiple light and dark phases can overcome the limitation of “snapshot” measurements in conventional behavioral assessments.…”

Section: Discussionmentioning

confidence: 99%

Long-Term Effects of Low-Intensity Blast Non-Inertial Brain Injury on Anxiety-Like Behaviors in Mice: Home-Cage Monitoring Assessments

Siedhoff

Chen

Balderrama

et al. 2022

Neurotrauma Reports

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Mild traumatic brain injury induced by low-intensity blast (LIB) exposure poses concerns in military personnel. Using an open-field, non-inertial blast model and assessments by conventional behavioral tests, our previous studies revealed early-phase anxiety-like behaviors in LIB-exposed mice. However, the impact of LIB upon long-term anxiety-like behaviors requires clarification. This study applied a highly sensitive automated home-cage monitoring (HCM) system, which minimized human intervention and environmental changes, to assess anxiety-like responses in mice 3 months after LIB exposure. Initial assessment of 72-h spontaneous activities in a natural cage condition over multiple light and dark phases showed altered sheltering behaviors. LIB-exposed mice exhibited a subtle, but significantly decreased, duration of short shelter visits as compared to sham controls. Other measured responses between LIB-exposed mice and sham controls were insignificant. When behavioral assessments were performed in a challenged condition using an aversive spotlight, LIB-exposed mice demonstrated a significantly higher frequency of movements of shorter distance and duration per movement. Taken together, these findings demonstrated the presence of chronic anxiety-like behaviors assessed by the HCM system under both natural and challenged conditions in mice occurring post-LIB exposure. This model thus provides a platform to test for screening and interventions on anxiety disorders occurring after LIB non-inertial brain injury.

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Section: Discussionmentioning

confidence: 99%

Long-Term Effects of Low-Intensity Blast Non-Inertial Brain Injury on Anxiety-Like Behaviors in Mice: Home-Cage Monitoring Assessments

Siedhoff

Chen

Balderrama

et al. 2022

Neurotrauma Reports

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“…As already mentioned, experimenter-induced animal stress caused by handling before and during testing, duration of testing, and exposure to new testing arenas may contribute to conflicting findings. Implementing automated behavioral assessments using home-cage monitoring with minimal human interference and animal stress appears to offer more consistent results ( 84 ).…”

Section: Translational Considerations Of Behavioral Impairmentsmentioning

confidence: 99%

Perspectives on Primary Blast Injury of the Brain: Translational Insights Into Non-inertial Low-Intensity Blast Injury

et al. 2022

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Most traumatic brain injuries (TBIs) during military deployment or training are clinically “mild” and frequently caused by non-impact blast exposures. Experimental models were developed to reproduce the biological consequences of high-intensity blasts causing moderate to severe brain injuries. However, the pathophysiological mechanisms of low-intensity blast (LIB)-induced neurological deficits have been understudied. This review provides perspectives on primary blast-induced mild TBI models and discusses translational aspects of LIB exposures as defined by standardized physical parameters including overpressure, impulse, and shock wave velocity. Our mouse LIB-exposure model, which reproduces deployment-related scenarios of open-field blast (OFB), caused neurobehavioral changes, including reduced exploratory activities, elevated anxiety-like levels, impaired nesting behavior, and compromised spatial reference learning and memory. These functional impairments associate with subcellular and ultrastructural neuropathological changes, such as myelinated axonal damage, synaptic alterations, and mitochondrial abnormalities occurring in the absence of gross- or cellular damage. Biochemically, we observed dysfunctional mitochondrial pathways that led to elevated oxidative stress, impaired fission-fusion dynamics, diminished mitophagy, decreased oxidative phosphorylation, and compensated cell respiration-relevant enzyme activity. LIB also induced increased levels of total tau, phosphorylated tau, and amyloid β peptide, suggesting initiation of signaling cascades leading to neurodegeneration. We also compare translational aspects of OFB findings to alternative blast injury models. By scoping relevant recent research findings, we provide recommendations for future preclinical studies to better reflect military-operational and clinical realities. Overall, better alignment of preclinical models with clinical observations and experience related to military injuries will facilitate development of more precise diagnosis, clinical evaluation, treatment, and rehabilitation.

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“…Mice learn that they will receive a sucrose pellet when they move through the holes in a certain pattern. Sucrose pellets are delivered automatically via the cage equipment and software script ( Heldring, 2019 ; Grieco et al, 2021 ). Wild-type mice learn this very quickly: at 12 weeks of age, they reach 80% correct entries within 6 h (i.e., within a single night).…”

Section: Evolution Of Digital Biomarkers From Short-lasting Tests To ...mentioning

confidence: 99%

“…Currently, the technology and use of DBs in a home cage is emerging and is still in early stages of development and implementation, with recent advances allowing for longitudinal and scalable digital monitoring of rodents across a range of disease models including neural, psychiatric, respiratory, and oncology ( Defensor et al, 2019 ; Baran et al, 2020 , 2021 ; Do et al, 2020 ; Golini et al, 2020 ; Hobson et al, 2020 ; Shenk et al, 2020 ; Voikar and Gaburro, 2020 ; Grieco et al, 2021 ). These emerging technologies provide an opportunity to modernize animal assessment and refine how preclinical in vivo data are collected, analyzed, and visualized.…”

Section: Introductionmentioning

confidence: 99%

Emerging Role of Translational Digital Biomarkers Within Home Cage Monitoring Technologies in Preclinical Drug Discovery and Development

Baran

Bratcher

Dennis

et al. 2022

Front. Behav. Neurosci.

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In drug discovery and development, traditional assessment of human patients and preclinical subjects occurs at limited time points in potentially stressful surroundings (i.e., the clinic or a test arena), which can impact data quality and welfare. However, recent advances in remote digital monitoring technologies enable the assessment of human patients and preclinical subjects across multiple time points in familiar surroundings. The ability to monitor a patient throughout disease progression provides an opportunity for more relevant and efficient diagnosis as well as improved assessment of drug efficacy and safety. In preclinical in vivo animal models, these digital technologies allow for continuous, longitudinal, and non-invasive monitoring in the home environment. This manuscript provides an overview of digital monitoring technologies for use in preclinical studies including their history and evolution, current engagement through use cases, and impact of digital biomarkers (DBs) on drug discovery and the 3Rs. We also discuss barriers to implementation and strategies to overcome them. Finally, we address data consistency and technology standards from the perspective of technology providers, end-users, and subject matter experts. Overall, this review establishes an improved understanding of the value and implementation of digital biomarker (DB) technologies in preclinical research.

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

Cited by 54 publications

References 235 publications

Long-Term Effects of Low-Intensity Blast Non-Inertial Brain Injury on Anxiety-Like Behaviors in Mice: Home-Cage Monitoring Assessments

Long-Term Effects of Low-Intensity Blast Non-Inertial Brain Injury on Anxiety-Like Behaviors in Mice: Home-Cage Monitoring Assessments

Perspectives on Primary Blast Injury of the Brain: Translational Insights Into Non-inertial Low-Intensity Blast Injury

Emerging Role of Translational Digital Biomarkers Within Home Cage Monitoring Technologies in Preclinical Drug Discovery and Development

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