Behavioral assays with mouse models of Alzheimer's disease: practical considerations and guidelines.
In Alzheimer's disease (AD) basic research and drug discovery, mouse models are essential resources for uncovering biological mechanisms, validating molecular targets and screening potential compounds. Both transgenic and non-genetically modified mouse models enable access to different types of AD-like pathology in vivo. Although there is a wealth of genetic and biochemical studies on proposed AD pathogenic pathways, as a disease that centrally features cognitive failure, the ultimate readout for any interventions should be measures of learning and memory. This is particularly important given the lack of knowledge on disease etiology - assessment by cognitive assays offers the advantage of targeting relevant memory systems without requiring assumptions about pathogenesis. A multitude of behavioral assays are available for assessing cognitive functioning in mouse models, including ones specific for hippocampal-dependent learning and memory. Here we review the basics of available transgenic and non-transgenic AD mouse models and detail three well-established behavioral tasks commonly used for testing hippocampal-dependent cognition in mice - contextual fear conditioning, radial arm water maze and Morris water maze. In particular, we discuss the practical considerations, requirements and caveats of these behavioral testing paradigms.
Department of Bio-Medical Sciences - Section of Physiology, University of Catania, Viale A. Doria 6, Catania 95125, Italy.
Daniela
D
Puzzo
Department of Pathology & Cell Biology, The Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, P&S #12-420D, 630W 168th Street, New York, NY 10032, USA.
Linda
L
Lee
Department of Bio-Medical Sciences - Section of Physiology, University of Catania, Viale A. Doria 6, Catania 95125, Italy.
Agostino
A
Palmeri
Department of Pharmacy, Federico II University, Via D. Montesano 49, Naples 80131, Italy.
Giorgio
G
Calabrese
Department of Pathology & Cell Biology, The Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, P&S #12-420D, 630W 168th Street, New York, NY 10032, USA. Electronic address: oa1@columbia.edu.
Ottavio
O
Arancio
D000544:Alzheimer Disease / Q000473:pathology / Q000503:physiopathology*; D000818:Animals; D001522:Behavior, Animal; D004195:Disease Models, Animal; D017408:Guidelines as Topic; D051379:Mice
Alzheimer's disease; Animal models; Behavior; Cognition; Memory