An approach to monitoring home-cage behavior in mice that facilitates data sharing

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An approach to monitoring home-cage behavior in mice that facilitates data sharing"


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ABSTRACT Genetically modified mice are used as models for a variety of human behavioral conditions. However, behavioral phenotyping can be a major bottleneck in mouse genetics because many


of the classic protocols are too long and/or are vulnerable to unaccountable sources of variance, leading to inconsistent results between centers. We developed a home-cage approach using a


Chora feeder that is controlled by—and sends data to—software. In this approach, mice are tested in the standard cages in which they are held for husbandry, which removes confounding


variables such as the stress induced by out-of-cage testing. This system increases the throughput of data gathering from individual animals and facilitates data mining by offering new


opportunities for multimodal data comparisons. In this protocol, we use a simple work-for-food testing strategy as an example application, but the approach can be adapted for other


experiments looking at, e.g., attention, decision-making or memory. The spontaneous behavioral activity of mice in performing the behavioral task can be monitored 24 h a day for several


days, providing an integrated assessment of the circadian profiles of different behaviors. We developed a Python-based open-source analytical platform (Phenopy) that is accessible to


scientists with no programming background and can be used to design and control such experiments, as well as to collect and share data. This approach is suitable for large-scale studies


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SIMILAR CONTENT BEING VIEWED BY OTHERS DATA REPURPOSING FROM DIGITAL HOME CAGE MONITORING ENLIGHTENS NEW PERSPECTIVES ON MOUSE MOTOR BEHAVIOUR AND REDUCTION PRINCIPLE Article Open access 05


July 2023 AN 8-CAGE IMAGING SYSTEM FOR AUTOMATED ANALYSES OF MOUSE BEHAVIOR Article Open access 19 May 2023 EVALUATION OF THE DIGITAL VENTILATED CAGE® SYSTEM FOR CIRCADIAN PHENOTYPING


Article Open access 29 January 2025 REFERENCES * Crabbe, J.C., Wahlsten, D. & Dudek, B.C. Genetics of mouse behavior: interactions with laboratory environment. _Science_ 284, 1670–1672


(1999). Article  CAS  PubMed  Google Scholar  * Almasy, L. & Blangero, J. Endophenotypes as quantitative risk factors for psychiatric disease: rationale and study design. _Am. J. Med.


Genet._ 105, 42–44 (2001). Article  CAS  PubMed  Google Scholar  * Gottesman, I.I. & Gould, T.D. The endophenotype concept in psychiatry: etymology and strategic intentions. _Am. J.


Psychiatry_ 160, 636–645 (2003). Article  PubMed  Google Scholar  * Glahn, D.C. et al. Arguments for the sake of endophenotypes: examining common misconceptions about the use of


endophenotypes in psychiatric genetics. _Am. J. Med. Genet. B Neuropsychiatr. Genet._ 165B, 122–130 (2014). Article  PubMed  CAS  Google Scholar  * Kas, M.J. & Van Ree, J.M. Dissecting


complex behaviours in the post-genomic era. _Trends Neurosci._ 27, 366–369 (2004). Article  CAS  PubMed  Google Scholar  * Papaleo, F., Lipska, B.K. & Weinberger, D.R. Mouse models of


genetic effects on cognition: relevance to schizophrenia. _Neuropharmacology_ 62, 1204–1220 (2012). Article  CAS  PubMed  Google Scholar  * Tucci, V., Lassi, G. & Kas, M.J. Current


understanding of the interplay between catechol-_O_-methyltransferase genetic variants, sleep, brain development and cognitive performance in schizophrenia. _CNS Neurol. Disord. Drug


Targets_ 11, 292–298 (2012). Article  CAS  PubMed  Google Scholar  * Papaleo, F., Burdick, M.C., Callicott, J.H. & Weinberger, D.R. Epistatic interaction between COMT and DTNBP1


modulates prefrontal function in mice and in humans. _Mol. Psychiatry_ 19, 311–316 (2014). Article  CAS  PubMed  Google Scholar  * Flint, J. & Munafo, M.R. The endophenotype concept in


psychiatric genetics. _Psychol. Med._ 37, 163–180 (2007). Article  PubMed  Google Scholar  * Munafo, M.R., Bowes, L., Clark, T.G. & Flint, J. Lack of association of the COMT (Val158/108


Met) gene and schizophrenia: a meta-analysis of case-control studies. _Mol. Psychiatry_ 10, 765–770 (2005). Article  CAS  PubMed  Google Scholar  * Bains, R.S. et al. Assessing mouse


behaviour throughout the light/dark cycle using automated in-cage analysis tools. _J. Neurosci. Methods_ 300, 37–47 (2017). Article  PubMed  Google Scholar  * Lassi, G. et al. Loss of Gnas


imprinting differentially affects REM/NREM sleep and cognition in mice. _PLoS Genet._ 8, e1002706 (2012). Article  CAS  PubMed  PubMed Central  Google Scholar  * Balzani, E. et al. The


Zfhx3-mediated axis regulates sleep and interval timing in mice. _Cell Rep._ 16, 615–621 (2016). Article  CAS  PubMed  PubMed Central  Google Scholar  * Tucci, V. et al. Dominant


beta-catenin mutations cause intellectual disability with recognizable syndromic features. _J. Clin. Invest._ 124, 1468–1482 (2014). Article  CAS  PubMed  PubMed Central  Google Scholar  *


Lassi, G. et al. Working-for-food behaviors: a preclinical study in Prader-Willi mutant mice. _Genetics_ 204, 1129–1138 (2016). Article  PubMed  PubMed Central  Google Scholar  * Maggi, S.


et al. A cross-laboratory investigation of timing endophenotypes in mouse behavior. _Timing Time Percept._ 2, 35–50 (2014). Article  Google Scholar  * Ward, R.D., Kellendonk, C., Kandel,


E.R. & Balsam, P.D. Timing as a window on cognition in schizophrenia. _Neuropharmacology_ 62, 1175–1181 (2012). Article  CAS  PubMed  Google Scholar  * Teixeira, S. et al. Time


perception distortion in neuropsychiatric and neurological disorders. _CNS Neurol. Disord. Drug Targets_ 12, 567–582 (2013). Article  CAS  PubMed  Google Scholar  * Hinton, S.C. et al. Motor


timing variability increases in preclinical Huntington's disease patients as estimated onset of motor symptoms approaches. _J. Int. Neuropsychol. Soc._ 13, 539–543 (2007). Article 


PubMed  Google Scholar  * Tinazzi, M. et al. Impaired temporal processing of tactile and proprioceptive stimuli in cerebellar degeneration. _PLoS One_ 8, e78628 (2013). Article  CAS  PubMed


  PubMed Central  Google Scholar  * Henley, S.M. et al. Degradation of cognitive timing mechanisms in behavioural variant frontotemporal dementia. _Neuropsychologia_ 65, 88–101 (2014).


Article  PubMed  PubMed Central  Google Scholar  * Crawley, J.N. Behavioral phenotyping strategies for mutant mice. _Neuron_ 57, 809–818 (2008). Article  CAS  PubMed  Google Scholar  *


Mandillo, S. et al. Reliability, robustness, and reproducibility in mouse behavioral phenotyping: a cross-laboratory study. _Physiol. Genomics_ 34, 243–255 (2008). Article  PubMed  PubMed


Central  Google Scholar  * Hart, P.C. et al. Experimental models of anxiety for drug discovery and brain research. _Methods Mol. Biol._ 602, 299–321 (2010). Article  CAS  PubMed  Google


Scholar  * Rosenthal, R. & Fode, K. The effect of experimenter bias on performance of the albino rat. _Behav. Sci._ 8, 183–189 (1963). Article  Google Scholar  * Holman, L., Head, M.L.,


Lanfear, R. & Jennions, M.D. Evidence of experimental bias in the life sciences: why we need blind data recording. _PLoS Biol._ 13, e1002190 (2015). Article  PubMed  PubMed Central  CAS


  Google Scholar  * Longordo, F., Fan, J., Steimer, T., Kopp, C. & Luthi, A. Do mice habituate to 'gentle handling?' A comparison of resting behavior, corticosterone levels and


synaptic function in handled and undisturbed C57BL/6J mice. _Sleep_ 34, 679–681 (2011). Article  PubMed  PubMed Central  Google Scholar  * Costa, R., Tamascia, M.L., Nogueira, M.D.,


Casarini, D.E. & Marcondes, F.K. Handling of adolescent rats improves learning and memory and decreases anxiety. _J. Am. Assoc. Lab. Anim. Sci._ 51, 548–553 (2012). CAS  PubMed  PubMed


Central  Google Scholar  * Tucci, V., Hardy, A. & Nolan, P.M. A comparison of physiological and behavioural parameters in C57BL/6J mice undergoing food or water restriction regimes.


_Behav. Brain Res._ 173, 22–29 (2006). Article  PubMed  Google Scholar  * Tucci, V. et al. Gene-environment interactions differentially affect mouse strain behavioral parameters. _Mamm.


Genome_ 17, 1113–1120 (2006). Article  PubMed  Google Scholar  * Frick, K.M., Stearns, N.A., Pan, J.Y. & Berger-Sweeney, J. Effects of environmental enrichment on spatial memory and


neurochemistry in middle-aged mice. _Learn. Mem._ 10, 187–198 (2003). Article  PubMed  PubMed Central  Google Scholar  * Jankowsky, J.L. et al. Environmental enrichment mitigates cognitive


deficits in a mouse model of Alzheimer's disease. _J. Neurosci._ 25, 5217–5224 (2005). Article  CAS  PubMed  PubMed Central  Google Scholar  * Rampon, C. et al. Enrichment induces


structural changes and recovery from nonspatial memory deficits in CA1 NMDAR1-knockout mice. _Nat. Neurosci._ 3, 238–244 (2000). Article  CAS  PubMed  Google Scholar  * van Praag, H.,


Kempermann, G. & Gage, F.H. Neural consequences of environmental enrichment. _Nat. Rev. Neurosci._ 1, 191–198 (2000). Article  CAS  PubMed  Google Scholar  * Tucci, V. et al. Reaching


and grasping phenotypes in the mouse (_Mus musculus_): a characterization of inbred strains and mutant lines. _Neuroscience_ 147, 573–582 (2007). Article  CAS  PubMed  Google Scholar  *


Balci, F., Freestone, D. & Gallistel, C.R. Risk assessment in man and mouse. _Proc. Natl. Acad. Sci. USA_ 106, 2459–2463 (2009). Article  CAS  PubMed  PubMed Central  Google Scholar  *


Balci, F. et al. High-throughput automated phenotyping of two genetic mouse models of Huntington's disease. _PLoS Curr._ 5


http://dx.doi.org/10.1371/currents.hd.124aa0d16753f88215776fba102ceb29 (2013). * Gallistel, C.R., Balci, F., Freestone, D., Kheifets, A. & King, A. Automated, quantitative


cognitive/behavioral screening of mice: for genetics, pharmacology, animal cognition and undergraduate instruction. _J. Vis. Exp._ (84)e51047 http://dx.doi.org/10.3791/51047 (2014). *


Cordes, S. & Gallistel, C.R. Intact interval timing in circadian CLOCK mutants. _Brain Res._ 1227, 120–127 (2008). Article  CAS  PubMed  PubMed Central  Google Scholar  * Perkel, J.M.


Programming: pick up Python. _Nature_ 518, 125–126 (2015). Article  CAS  PubMed  Google Scholar  * Dunlap, J.C. Molecular bases for circadian clocks. _Cell_ 96, 271–290 (1999). Article  CAS


  PubMed  Google Scholar  * Mohawk, J.A. & Takahashi, J.S. Cell autonomy and synchrony of suprachiasmatic nucleus circadian oscillators. _Trends Neurosci._ 34, 349–358 (2011). Article 


CAS  PubMed  PubMed Central  Google Scholar  * Balci, F. et al. Interval timing in genetically modified mice: a simple paradigm. _Genes Brain Behav._ 7, 373–384 (2008). Article  CAS  PubMed


  Google Scholar  * Cheng, K., Westwood, R. & Crystal, J.D. Memory variance in the peak procedure of timing in pigeons. _J. Exp. Psychol. Anim. Behav. Process._ 19, 68–76 (1993). Article


  Google Scholar  * Church, R.M., Meck, W.H. & Gibbon, J. Application of scalar timing theory to individual trials. _J. Exp. Psychol. Anim. Behav. Process._ 20, 135–155 (1994). Article 


CAS  PubMed  Google Scholar  * Balci, F. et al. Acquisition of peak responding: what is learned? _Behav. Process._ 80, 67–75 (2009). Article  Google Scholar  * Feldmann, H.M., Golozoubova,


V., Cannon, B. & Nedergaard, J. UCP1 ablation induces obesity and abolishes diet-induced thermogenesis in mice exempt from thermal stress by living at thermoneutrality. _Cell Metab._ 9,


203–209 (2009). Article  CAS  PubMed  Google Scholar  * Lassi, G. et al. Deletion of the Snord116/SNORD116 alters sleep in mice and patients with Prader-Willi syndrome. _Sleep_ 39, 637–644


(2016). Article  PubMed  PubMed Central  Google Scholar  * Balzani, E. et al. The Zfhx3-mediated axis regulates sleep and interval timing in mice. _Cell Rep._ 16(3), 615–621 (2016). Article


  CAS  Google Scholar  * Tosun, T., Gür, F. & Balci, F. Mice plan decision strategies based on previously learned time intervals, locations, and probabilities. _Proc. Natl. Acad. Sci.


USA_ 113, 787–792 (2016). Article  CAS  PubMed  PubMed Central  Google Scholar  * Rossi, M.A. & Yin, H.H. Methods for studying habitual behavior in mice. _Curr. Protoc. Neurosci._ Chap.


8, Unit 8.29 (2012). * Aquili, L. et al. Behavioral flexibility is increased by optogenetic inhibition of neurons in the nucleus accumbens shell during specific time segments. _Learn. Mem._


21(4), 223–231 (2014). Article  Google Scholar  * Cottrell, J.R. et al. Working memory impairment in calcineurin knock-out mice is associated with alterations in synaptic vesicle cycling and


disruption of high-frequency synaptic and network activity in prefrontal cortex. _J. Neurosci._ 33(27) 10938–10949 (2013). Article  CAS  Google Scholar  * Bach, M.E. et al. Transient and


selective overexpression of D2 receptors in the striatum causes persistent deficits in conditional associative learning. _Proc. Natl. Acad. Sci._ 105 16027–16032 (2008). Article  CAS  PubMed


  PubMed Central  Google Scholar  * Papachristos, E.B. & Gallistel, C.R. Autoshaped head poking in the mouse: a quantitative analysis of the learning curve. _J. Exp. Anal. Behav._ 85,


293–308 (2006). Article  PubMed  PubMed Central  Google Scholar  * Gallistel, C.R. et al. Is matching innate? _J. Exp. Anal. Behav._ 87, 161–199 (2007). Article  CAS  PubMed  PubMed Central


  Google Scholar  * Pinkston, J.W. & Lamb, R.J. Delay discounting in C57BL/6J and DBA/2J mice: adolescent-limited and life-persistent patterns of impulsivity. _Behav. Neurosci._ 125,


194–201 (2011). Article  PubMed  PubMed Central  Google Scholar  * Young, J.W., Light, G.A., Marston, H.M., Sharp, R. & Geyer, M.A. The 5-choice continuous performance test: evidence for


a translational test of vigilance for mice. _PLoS One_ 4 e4227 (2009). * Gourley, S.L. et al. Dissociable regulation of instrumental action within mouse prefrontal cortex. _Eur. J.


Neurosci._ 32, 1726–1734 (2010). Article  PubMed  PubMed Central  Google Scholar  Download references ACKNOWLEDGEMENTS We thank the IT group at the IIT for technical support. This study was


supported by the European Commission FP7 Programme under project 223263 (PhenoScale). AUTHOR INFORMATION Author notes * Edoardo Balzani and Matteo Falappa: These authors contributed equally


to this work. AUTHORS AND AFFILIATIONS * Department of Neuroscience and Brain Technologies, Istituto Italiano di Tecnologia, Genova, Italy Edoardo Balzani, Matteo Falappa & Valter Tucci


* Dipartimento di Neuroscienze, Riabilitazione, Oftalmologia, Genetica e Scienze Materno-Infantili (DINOGMI), Università degli Studi di Genova, Genova, Italy Matteo Falappa * Department of


Psychology, Koç University, Istanbul, Turkey Fuat Balci * Research Center for Translational Medicine, Koç University, Istanbul, Turkey Fuat Balci Authors * Edoardo Balzani View author


publications You can also search for this author inPubMed Google Scholar * Matteo Falappa View author publications You can also search for this author inPubMed Google Scholar * Fuat Balci


View author publications You can also search for this author inPubMed Google Scholar * Valter Tucci View author publications You can also search for this author inPubMed Google Scholar


CONTRIBUTIONS E.B. and M.F. wrote Phenopy and performed the experiments and the analyses. F.B. designed the original timing analyses. V.T. conceived, planned and supervised the project, and


wrote the manuscript with the help of all co-authors. CORRESPONDING AUTHOR Correspondence to Valter Tucci. ETHICS DECLARATIONS COMPETING INTERESTS The authors declare no competing financial


interests. INTEGRATED SUPPLEMENTARY INFORMATION SUPPLEMENTARY FIGURE 1 TOP VIEW OF CHORA FEEDERS This picture shows the top panel of the CHORA feeders. The power lever and the operational


mode lever are indicated by a red arrow. The lever of the operational state is set in via cable modality. Switch the lever for wireless mode. Once the feeder is turned on, the communication


modality cannot be changed. To change the communication modality, first switch off the feeder and then change the communication modality. SUPPLEMENTARY INFORMATION SUPPLEMENTARY TEXT AND


FIGURES Supplementary Figure 1, Supplementary Methods and Supplementary Tables 1 and 2. (PDF 763 kb) SUPPLEMENTARY DATA Recorded data and Python example scripts. (ZIP 117880 kb) RUNNING


PHENOPY. This video shows how to set up a behavioral experimental protocol using Chora feeders and Phenopy. (MP4 4370 kb) DATA ANALYSIS EXAMPLE. This video shows how to import, export, edit


and analyze data using Phenopy. (MOV 4714 kb) IMPORTING FUNCTIONS. This video shows how to upload a new importation function into Phenopy. (MOV 2841 kb) IMPORTING A NEW ANALYSIS. This video


shows how to upload a new analysis function into Phenopy. (MOV 4635 kb) RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Balzani, E., Falappa, M., Balci,


F. _et al._ An approach to monitoring home-cage behavior in mice that facilitates data sharing. _Nat Protoc_ 13, 1331–1347 (2018). https://doi.org/10.1038/nprot.2018.031 Download citation *


Published: 17 May 2018 * Issue Date: June 2018 * DOI: https://doi.org/10.1038/nprot.2018.031 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this content:


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