title: The light spot test: Measuring anxiety in mice in an automated home-cage environment.
abstract: Behavioral tests of animals in a controlled experimental setting provide a valuable tool to advance understanding of genotype-phenotype relations, and to study the effects of genetic and environmental manipulations. To optimally benefit from the increasing numbers of genetically engineered mice, reliable high-throughput methods for comprehensive behavioral phenotyping of mice lines have become a necessity. Here, we describe the development and validation of an anxiety test, the light spot test, that allows for unsupervised, automated, high-throughput testing of mice in a home-cage system. This automated behavioral test circumvents bias introduced by pretest handling, and enables recording both baseline behavior and the behavioral test response over a prolonged period of time. We demonstrate that the light spot test induces a behavioral response in C57BL/6J mice. This behavior reverts to baseline when the aversive stimulus is switched off, and is blunted by treatment with the anxiolytic drug Diazepam, demonstrating predictive validity of the assay, and indicating that the observed behavioral response has a significant anxiety component. Also, we investigated the effectiveness of the light spot test as part of sequential testing for different behavioral aspects in the home-cage. Two learning tests, administered prior to the light spot test, affected the light spot test parameters. The light spot test is a novel, automated assay for anxiety-related high-throughput testing of mice in an automated home-cage environment, allowing for both comprehensive behavioral phenotyping of mice, and rapid screening of pharmacological compounds.
authors.affiliation: Section Functional Genomics, Center for Neurogenomics and Cognitive Research, VU University Amsterdam, de Boelelaan 1085, 1081HV, Amsterdam, The Netherlands.
authors.forename: Emmeke
authors.initials: E
authors.lastname: Aarts
authors.affiliation: Section Functional Genomics, Center for Neurogenomics and Cognitive Research, VU University Amsterdam, de Boelelaan 1085, 1081HV, Amsterdam, The Netherlands.
authors.forename: Gregoire
authors.initials: G
authors.lastname: Maroteaux
authors.affiliation: Sylics (Snypatologics BV), PO box 71033, 1008 BA, Amsterdam, The Netherlands; Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, VU University Amsterdam, de Boelelaan 1085, 1081HV, The Netherlands.
authors.forename: Maarten
authors.initials: M
authors.lastname: Loos
authors.affiliation: Sylics (Snypatologics BV), PO box 71033, 1008 BA, Amsterdam, The Netherlands.
authors.forename: Bastijn
authors.initials: B
authors.lastname: Koopmans
authors.affiliation: Section Functional Genomics, Center for Neurogenomics and Cognitive Research, VU University Amsterdam, de Boelelaan 1085, 1081HV, Amsterdam, The Netherlands.
authors.forename: Jovana
authors.initials: J
authors.lastname: Kovačević
authors.affiliation: Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, VU University Amsterdam, de Boelelaan 1085, 1081HV, The Netherlands.
authors.forename: August B
authors.initials: AB
authors.lastname: Smit
authors.affiliation: Section Functional Genomics, Center for Neurogenomics and Cognitive Research, VU University Amsterdam, de Boelelaan 1085, 1081HV, Amsterdam, The Netherlands; Section Functional Genomics, Department Clinical Genetics, VU Medical Center, de Boelelaan 1085, 1081HV, Amsterdam, The Netherlands. Electronic address: m.verhage@vu.nl.
authors.forename: Matthijs
authors.initials: M
authors.lastname: Verhage
authors.affiliation: Section Complex Trait Genetics, Department of Clinical Genetics, VU Medical Center, de Boelelaan 1085, 1081HV, Amsterdam, The Netherlands.
authors.forename: Sophie van der
authors.initials: Sv
authors.lastname: Sluis
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology; D001007:Anxiety / Q000175:diagnosis* / Q000188:drug therapy; D057205:Automation, Laboratory / Q000295:instrumentation* / Q000379:methods; D003975:Diazepam / Q000494:pharmacology; D004867:Equipment Design; D006799:Housing, Animal; D008027:Light; D008297:Male; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D010775:Photic Stimulation / Q000295:instrumentation* / Q000379:methods; D011581:Psychological Tests
chemical_list: D014151:Anti-Anxiety Agents; D003975:Diazepam
keywords: Anxiety; Automated home-cage testing; Behavioral phenotyping; Diazepam; Mice; Sequential testing