Effects of fimbria-fornix lesion and amyloid pathology on spatial learning and memory in transgenic APP+PS1 mice.
Transgenic mice carrying mutated human amyloid precursor protein (APPswe) and presenilin (PS1, A246E) genes develop first amyloid plaques around 9 months of age, but up to 18 months of age, amyloid depositions in these mice were largely restricted to the hippocampus, subiculum, and neocortex. To assess the behavioral consequences of amyloid accumulation in the hippocampal formation, we compared the effects of APP+PS1 (AP) genotype and fimbria-fornix (FFX) transection, either alone or combined, on various spatial learning and memory tasks. Both FFX-lesioned and AP mice were impaired in spatial navigation in the water maze, a typical hippocampal dependent task. Conversely, neither group of mice was impaired in a win-stay version of the radial arm maze (RAM) or position discrimination in the T-maze, tasks that do not depend on the hippocampus. FFX-lesioned mice were impaired in the win-shift version of the RAM, and in spontaneous and rewarded alternation in the T-maze, while AP mice performed equal to non-transgenic controls in all these working memory tasks, except long-term retention of the RAM task. AP mice thus appear to have a selective deficit in hippocampal dependent long-term memory, as do Alzheimer patients at early stage of the disease.
Department of Neuroscience and Neurology, University of Kuopio/Canthia, PO Box 1627, 70211 Kuopio, Finland.
Li
L
Liu
Sami
S
Ikonen
Taneli
T
Heikkinen
Matti
M
Heikkilä
Jukka
J
Puoliväli
Thomas
T
van Groen
Heikki
H
Tanila
D000679:Amygdala / Q000378:metabolism / Q000502:physiology*; D017772:Amyloid Neuropathies / Q000235:genetics / Q000378:metabolism / Q000523:psychology*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D001007:Anxiety / Q000235:genetics / Q000523:psychology; D001923:Brain Chemistry / Q000502:physiology; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D020712:Fornix, Brain / Q000502:physiology*; D018782:Maze Learning / Q000502:physiology; D008565:Membrane Proteins / Q000235:genetics*; D008568:Memory / Q000502:physiology*; D008570:Memory, Short-Term / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D053764:Presenilin-1; D013028:Space Perception / Q000502:physiology*
D016564:Amyloid beta-Protein Precursor; D008565:Membrane Proteins; C508853:PSEN1 protein, human; D053764:Presenilin-1; D002795:Choline O-Acetyltransferase