Novel age-dependent learning deficits in a mouse model of Alzheimer's disease: Implications for translational research

NEUROBIOLOGY OF AGING

卷:32

Article

Montgomery, K. S.¹  Simmons, R. K.¹  Edwards, G., III¹  Nicolle, M. M.³  Gluck, M. A.⁴  Myers, C. E.⁵  Bizon, J. L.^1,2 

[1] Texas A&M Univ, Dept Psychol, College Stn, TX 77843 USA

[2] Texas A&M Univ, Fac Neurosci, College Stn, TX 77843 USA

[3] Wake Forest Univ, Bowman Gray Sch Med, Dept Physiol & Pharmacol, Winston Salem, NC 27157 USA

[4] Rutgers State Univ, Ctr Mol & Behav Neurosci, Newark, NJ 07102 USA

[5] Rutgers State Univ, Dept Psychol, Newark, NJ 08854 USA

关键词: Aging;    AD;    APP+PS1;    Hippocampus;    Transfer learning;    Spatial learning;    Cognitive decline;   

DOI  :  10.1016/j.neurobiolaging.2009.08.003

来源: Elsevier

【 摘 要 】

Computational modeling predicts that the hippocampus plays an important role in the ability to apply previously learned information to novel problems and situations (referred to as the ability to generalize information or simply as 'transfer learning'). These predictions have been tested in humans using a computer-based task on which individuals with hippocampal damage are able to learn a series of complex discriminations with two stimulus features (shape and color), but are impaired in their ability to transfer this information to newly configured problems in which one of the features is altered. This deficit occurs despite the fact that the feature predictive of the reward (the relevant information) is not changed. The goal of the current study was to develop a mouse analog of transfer learning and to determine if this new task was sensitive to pathological changes in a mouse model of AD. We describe a task in which mice were able to learn a series of concurrent discriminations that contained two stimulus features (odor and digging media) and could transfer this learned information to new problems in which the irrelevant feature in each discrimination pair was altered. Moreover, we report age-dependent deficits specific to transfer learning in APP + PS1 mice relative to non-transgenic littermates. The robust impairment in transfer learning may be more sensitive to AD-like pathology than traditional cognitive assessments in that no deficits were observed in the APP + PS1 mice on the widely used Morris water maze task. These data describe a novel and sensitive paradigm to evaluate mnemonic decline in AD mouse models that has unique translational advantages over standard species-specific cognitive assessments (e.g., water maze for rodent and delayed paragraph recall for humans). (C) 2009 Elsevier Inc. All rights reserved.

【 授权许可】

Free