title: Measuring discrimination- and reversal learning in mouse models within 4 days and without prior food deprivation.
abstract: Many neurological and psychiatric disorders are characterized by deficits in cognitive flexibility. Modeling cognitive flexibility in mice enables the investigation of mechanisms underlying these deficits. The majority of currently available behavioral tests targeting this cognitive domain are reversal learning tasks that require scheduled food restriction, extended training periods and labor-intensive, and stress-inducing animal handling. Here, we describe a novel 4-day (4-d) continuously running task measuring discrimination- and reversal learning in an automated home cage (CognitionWall DL/RL task) that largely eliminates these limitations. In this task, mice can earn unlimited number of food rewards by passing through the correct hole of the three-holed CognitionWall. To assess the validity and sensitivity of this novel task, the performance of C57BL/6J mice, amyloid precursor protein/presenilin1 transgenic (APP/PS1) mice, α-calmodulin kinase-II (αCaMKII) T305D knock-in mice, and mice with an orbitofrontal cortex lesion were examined. We found that C57BL/6J mice reach stable performance levels within the 4 d of the task, while experiencing only slight reductions in weight and no major effects on circadian rhythm. The task detected learning deficits in APP/PS1 transgenic and αCaMKII T305D mutant mice. Additionally, we established that the orbitofrontal cortex underlies reversal learning performance in our task. Because of its short duration and the absence of food deprivation and concurrent weight loss, this novel automated home-cage task substantially improves comprehensive preclinical assessment of cognitive functions in mouse models of psychiatric and neurological disorders and also enables analysis during specific developmental stages.
authors.affiliation: Sylics (Synaptologics B.V.), 1008 BA Amsterdam, The Netherlands.|Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University, 1081 HV Amsterdam, The Netherlands.|Department of Functional Genomics, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University, 1081 HV Amsterdam, The Netherlands.
authors.forename: Esther
authors.identifier: 0000-0002-8227-8748
authors.initials: E
authors.lastname: Remmelink
authors.affiliation: Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University, 1081 HV Amsterdam, The Netherlands.
authors.forename: August B
authors.initials: AB
authors.lastname: Smit
authors.affiliation: Department of Functional Genomics, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University, 1081 HV Amsterdam, The Netherlands.
authors.forename: Matthijs
authors.initials: M
authors.lastname: Verhage
authors.affiliation: Sylics (Synaptologics B.V.), 1008 BA Amsterdam, The Netherlands maarten.loos@sylics.com.
authors.forename: Maarten
authors.initials: M
authors.lastname: Loos
mesh_terms: D000375:Aging / Q000523:psychology; D000818:Animals; D057205:Automation, Laboratory; D004192:Discrimination, Psychological / Q000502:physiology; D005502:Food; D006799:Housing, Animal; D053208:Kaplan-Meier Estimate; D007859:Learning Disabilities / Q000209:etiology / Q000503:physiopathology; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D023421:Models, Animal; D017397:Prefrontal Cortex / Q000503:physiopathology; D011581:Psychological Tests; D012193:Reversal Learning / Q000502:physiology; D013997:Time Factors