title: 16p11.2 Deletion mice display cognitive deficits in touchscreen learning and novelty recognition tasks.
abstract: Chromosomal 16p11.2 deletion syndrome frequently presents with intellectual disabilities, speech delays, and autism. Here we investigated the Dolmetsch line of 16p11.2 heterozygous (+/-) mice on a range of cognitive tasks with different neuroanatomical substrates. Robust novel object recognition deficits were replicated in two cohorts of 16p11.2+/- mice, confirming previous findings. A similarly robust deficit in object location memory was discovered in +/-, indicating impaired spatial novelty recognition. Generalizability of novelty recognition deficits in +/- mice extended to preference for social novelty. Robust learning deficits and cognitive inflexibility were detected using Bussey-Saksida touchscreen operant chambers. During acquisition of pairwise visual discrimination, +/- mice required significantly more training trials to reach criterion than wild-type littermates (+/+), and made more errors and correction errors than +/+. In the reversal phase, all +/+ reached criterion, whereas most +/- failed to reach criterion by the 30-d cutoff. Contextual and cued fear conditioning were normal in +/-. These cognitive phenotypes may be relevant to some aspects of cognitive impairments in humans with 16p11.2 deletion, and support the use of 16p11.2+/- mice as a model system for discovering treatments for cognitive impairments in 16p11.2 deletion syndrome.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, MIND Institute, University of California Davis School of Medicine, Sacramento, California 95817, USA muyang@ucdavis.edu.
authors.forename: Mu
authors.initials: M
authors.lastname: Yang
authors.affiliation: Department of Psychiatry and Behavioral Sciences, MIND Institute, University of California Davis School of Medicine, Sacramento, California 95817, USA.
authors.forename: Freeman C
authors.initials: FC
authors.lastname: Lewis
authors.affiliation: Department of Psychiatry and Behavioral Sciences, MIND Institute, University of California Davis School of Medicine, Sacramento, California 95817, USA.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Sarvi
authors.affiliation: Department of Psychiatry and Behavioral Sciences, MIND Institute, University of California Davis School of Medicine, Sacramento, California 95817, USA.
authors.forename: Gillian M
authors.initials: GM
authors.lastname: Foley
authors.affiliation: Department of Psychiatry and Behavioral Sciences, MIND Institute, University of California Davis School of Medicine, Sacramento, California 95817, USA.
authors.forename: Jacqueline N
authors.initials: JN
authors.lastname: Crawley
mesh_terms: D000818:Animals; D001321:Autistic Disorder / Q000150:complications* / Q000503:physiopathology / Q000523:psychology*; D002872:Chromosome Deletion; D025063:Chromosome Disorders / Q000150:complications* / Q000503:physiopathology / Q000523:psychology*; D002885:Chromosomes, Human, Pair 16; D003072:Cognition Disorders / Q000209:etiology* / Q000235:genetics; D003213:Conditioning, Psychological; D003463:Cues; D004192:Discrimination, Psychological; D005239:Fear; D005260:Female; D006579:Heterozygote; D008607:Intellectual Disability / Q000150:complications* / Q000503:physiopathology / Q000523:psychology*; D007858:Learning; D007859:Learning Disabilities / Q000209:etiology / Q000235:genetics; D008297:Male; D008822:Mice, Transgenic; D011581:Psychological Tests; D021641:Recognition, Psychology; D012193:Reversal Learning; D012938:Social Perception; D065852:Spatial Memory; D013550:Swimming; D014796:Visual Perception