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      Assessing mouse behaviour throughout the light/dark cycle using automated in-cage analysis tools

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          Highlights

          • Automated assessment of mouse home-cage behaviour is robust and reliable.

          • Analysis over multiple light/dark cycles improves ability to classify behaviours.

          • Combined RFID and video analysis enables home-cage analysis in group housed animals.

          Abstract

          An important factor in reducing variability in mouse test outcomes has been to develop assays that can be used for continuous automated home cage assessment. Our experience has shown that this has been most evidenced in long-term assessment of wheel-running activity in mice. Historically, wheel-running in mice and other rodents have been used as a robust assay to determine, with precision, the inherent period of circadian rhythms in mice. Furthermore, this assay has been instrumental in dissecting the molecular genetic basis of mammalian circadian rhythms. In teasing out the elements of this test that have determined its robustness – automated assessment of an unforced behaviour in the home cage over long time intervals – we and others have been investigating whether similar test apparatus could be used to accurately discriminate differences in distinct behavioural parameters in mice. Firstly, using these systems, we explored behaviours in a number of mouse inbred strains to determine whether we could extract biologically meaningful differences. Secondly, we tested a number of relevant mutant lines to determine how discriminative these parameters were. Our findings show that, when compared to conventional out-of-cage phenotyping, a far deeper understanding of mouse mutant phenotype can be established by monitoring behaviour in the home cage over one or more light:dark cycles.

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          Behavioural phenotyping assays for mouse models of autism.

          Autism is a heterogeneous neurodevelopmental disorder of unknown aetiology that affects 1 in 100-150 individuals. Diagnosis is based on three categories of behavioural criteria: abnormal social interactions, communication deficits and repetitive behaviours. Strong evidence for a genetic basis has prompted the development of mouse models with targeted mutations in candidate genes for autism. As the diagnostic criteria for autism are behavioural, phenotyping these mouse models requires behavioural assays with high relevance to each category of the diagnostic symptoms. Behavioural neuroscientists are generating a comprehensive set of assays for social interaction, communication and repetitive behaviours to test hypotheses about the causes of autism. Robust phenotypes in mouse models hold great promise as translational tools for discovering effective treatments for components of autism spectrum disorders.
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            Genetics of mouse behavior: interactions with laboratory environment.

            Strains of mice that show characteristic patterns of behavior are critical for research in neurobehavioral genetics. Possible confounding influences of the laboratory environment were studied in several inbred strains and one null mutant by simultaneous testing in three laboratories on a battery of six behaviors. Apparatus, test protocols, and many environmental variables were rigorously equated. Strains differed markedly in all behaviors, and despite standardization, there were systematic differences in behavior across labs. For some tests, the magnitude of genetic differences depended upon the specific testing lab. Thus, experiments characterizing mutants may yield results that are idiosyncratic to a particular laboratory.
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              Emergence of individuality in genetically identical mice.

              Brain plasticity as a neurobiological reflection of individuality is difficult to capture in animal models. Inspired by behavioral-genetic investigations of human monozygotic twins reared together, we obtained dense longitudinal activity data on 40 inbred mice living in one large enriched environment. The exploratory activity of the mice diverged over time, resulting in increasing individual differences with advancing age. Individual differences in cumulative roaming entropy, indicating the active coverage of territory, correlated positively with individual differences in adult hippocampal neurogenesis. Our results show that factors unfolding or emerging during development contribute to individual differences in structural brain plasticity and behavior. The paradigm introduced here serves as an animal model for identifying mechanisms of plasticity underlying nonshared environmental contributions to individual differences in behavior.
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                Author and article information

                Contributors
                Journal
                J Neurosci Methods
                J. Neurosci. Methods
                Journal of Neuroscience Methods
                Elsevier/North-Holland Biomedical Press
                0165-0270
                1872-678X
                15 April 2018
                15 April 2018
                : 300
                : 37-47
                Affiliations
                [a ]Mary Lyon Centre, MRC Harwell Institute, Harwell Science Campus, Oxfordshire, UK
                [b ]Mammalian Genetics Unit, MRC Harwell Institute, Harwell Science Campus, Oxfordshire, UK
                [c ]Actual Analytics Ltd., Edinburgh, UK
                [d ]School of Informatics, University of Edinburgh, Edinburgh, UK
                Author notes
                [* ]Corresponding author at: Mammalian Genetics Unit, MRC Harwell Institute, Harwell Science Campus, Oxfordshire, OX11 0RD, UK. p.nolan@ 123456har.mrc.ac.uk
                Article
                S0165-0270(17)30113-9
                10.1016/j.jneumeth.2017.04.014
                5909039
                28456660
                9ff8c0ea-9da9-4d4b-825c-8abeac3417d7
                © 2017 The Author(s)

                This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

                History
                : 14 February 2017
                : 21 April 2017
                : 22 April 2017
                Categories
                Article

                Neurosciences
                home cage,welfare,circadian,motor function,refinement,wheel running
                Neurosciences
                home cage, welfare, circadian, motor function, refinement, wheel running

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