A novel operant testing regimen for multi-construct cognitive characterization of a murine model of Alzheimer’s amyloid-related behavioral impairment

• Published in: Neurobiology of learning and memory Vol. 96; no. 3; pp. 443 - 451
• Main Authors: Blackshear, Alice L., Xu, Wenjin, Anderson, Maria, Xu, Feng, Previti, Mary Lou, Van Nostrand, William E., Robinson, John K.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 01.10.2011; Elsevier; Elsevier BV
• Subjects: Adult and adolescent clinical studies; Alzheimer Disease - physiopathology; Alzheimer's disease; Analysis of Variance; Animal behavior; Animal cognition; Animals; Association Learning - physiology; Behavior, Animal; Behavioral psychophysiology; Biological and medical sciences; Brain; Cognition - physiology; Conditioning, Operant - physiology; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Discrimination Learning - physiology; Disease Models, Animal; Female; Fundamental and applied biological sciences. Psychology; Learning; Male; Medical sciences; Memory; Mice; Mice, Transgenic; Motivation; Neurobiology; Neurology; Operant; Organic mental disorders. Neuropsychology; Psychology. Psychoanalysis. Psychiatry; Psychology. Psychophysiology; Psychopathology. Psychiatry; Rodents; Tg2576; Transgenic; Learning; Transgenic; Memory; Operant; Tg2576; Nervous system diseases; Alzheimer disease; Transgenic animal; Cognition; Cerebral disorder; Characterization; Acquisition process; Central nervous system disease; Degenerative disease; Amyloid; Models; Behavior
• ISSN: 1074-7427; 1095-9564; 1095-9564
• DOI: 10.1016/j.nlm.2011.06.017

► This study presents a novel operant behavioral methodology for testing transgenic murine models of Alzheimer’s disease. ► Tg2576 mice experienced a progressively more complex and inter-supporting battery of operant tasks. ► Attrition from the study correlated with increasing task demands and amyloid load. A common method for modeling pathological and behavioral aspects of Alzheimer’s disease (AD) is the transgenic mouse. While transgenic strains are often well characterized pathologically, behavioral studies of cognitive deficits often employ a limited set of aversively motivated, spatial learning and memory tests, under brief testing periods. Here we illustrate an alternative operant behavioral methodology to provide a comprehensive characterization under repetitive testing conditions, and with appetitive motivation. In this study, we employed the commonly used Tg2576 murine model of Alzheimer’s disease amyloid pathology, since it has been the subject of many previous behavioral studies. In these mice, we compared the learning of simple and complex, as well as spatial and non-spatial rules. The mice were assessed on a progressively more complex and interlocking battery of operant tasks, ranging from simple rule learning to delayed recall, as well as tests of motor and sensory ability. In general, as compared to wild type control mice, within-group variability was high in the Tg2576 mice, and deficits were most apparent in more complex discrimination tasks. Furthermore, a consistent decrease in the rate at which Tg2576 mice completed testing trials was observed, pointing to a potential motivation difference or speed–accuracy tradeoffs as a defining characteristic of this strain under these test conditions. Using sensitive adjusting retention interval procedures, it was also possible to isolate a difference in retention interval and separate it from non-mnemonic processes. Overall, these experiments demonstrate the utility of this novel operant approach for characterizing the cognitive deficits of transgenic murine models of dementia.