Altered navigational strategy use and visuospatial deficits in hAPP transgenic mice.
Navigation deficits are prominent in Alzheimer's disease (AD) patients and transgenic mice expressing familial AD-mutant hAPP and A beta peptides. To determine the impact of strategy use on these deficits, we assessed hAPP and nontransgenic mice in a cross maze that can be solved by allocentric (world-based) or egocentric (self-based) strategies. Most nontransgenic mice used allocentric strategies, whereas half of hAPP mice were egocentric. At 3 months, all mice learned the cross maze rapidly; at 6 months, only allocentric hAPP mice were impaired. At 3 and 6 months, hAPP mice had reduced hippocampal Fos expression, which correlated with cross maze learning in older mice. Striatal pCREB expression was unaltered in hAPP mice, suggesting striatal sparing. We conclude that egocentric strategy use may be an earlier indicator of hAPP/A beta-induced hippocampal impairment than spatial learning deficits. Persistent use of allocentric strategies when egocentric strategies are available is maladaptive when there is hippocampal damage. Interventions promoting flexibility in selecting learning strategies might help circumvent otherwise debilitating navigational deficits caused by AD-related hippocampal dysfunction.
Deipolyi
Amy R
AR
Gladstone Institute of Neurological Disease, 1650 Owens Street, San Francisco, CA 94158, USA.
Fang
Shanna
S
Palop
Jorge J
JJ
Yu
Gui-Qiu
GQ
Wang
Xin
X
Mucke
Lennart
L
D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D000818:Animals; D001522:Behavior, Animal; D002755:Choice Behavior / Q000502:physiology; D003342:Corpus Striatum / Q000378:metabolism; D003463:Cues; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D007859:Learning Disabilities / Q000235:genetics; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D009949:Orientation / Q000502:physiology*; D010468:Perceptual Disorders / Q000235:genetics*; D013028:Space Perception / Q000502:physiology*; D013037:Spatial Behavior / Q000502:physiology*; D014792:Visual Acuity / Q000235:genetics
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor