Accelerated extinction of conditioned taste aversion in P301L tau transgenic mice.
Neurofibrillary tangles, insoluble protein deposits composed of filamentous tau aggregates, are neuropathological hallmarks of Alzheimer's disease and familial frontotemporal dementia (FTDP-17). Transgenic mice expressing the FTDP-17 mutation P301L of tau recapitulate key features of the human pathology, that is, tau proteins aggregate and neurofibrillary tangles begin to appear in the amygdala at 6 months of age. To detect early signs of tau aggregate-associated changes, we investigated behavioral alterations and cognitive deficits in such mice using an amygdala-specific test battery for anxiety-related and cognitive behavior. P301L mice had anxiety levels not different from wild-types, but their exploratory behavior was significantly increased. Acquisition of a fear response to tone and context as well as taste aversion was comparable to wild-types. However, extinction of a conditioned taste aversion was significantly accelerated. We conclude that already aggregation of tau proteins not yet accompanied by massive formation of neurofibrillary tangles causes selective behavioral deficits.
Pennanen
Luis
L
Division of Psychiatry Research, University of Zürich, 8008 Zürich, Switzerland.
Welzl
Hans
H
D'Adamo
Patrizia
P
Nitsch
Roger M
RM
Götz
Jürgen
J
D000818:Animals; D001007:Anxiety; D001522:Behavior, Animal / Q000502:physiology*; D001921:Brain / Q000473:pathology* / Q000502:physiology; D003214:Conditioning, Classical / Q000502:physiology; D004195:Disease Models, Animal; D005108:Extinction, Psychological / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D008869:Microtubule-Associated Proteins / Q000235:genetics*; D019636:Neurodegenerative Diseases / Q000235:genetics; D016874:Neurofibrillary Tangles / Q000473:pathology; D013649:Taste / Q000502:physiology; D016875:tau Proteins / Q000096:biosynthesis / Q000235:genetics*
C054369:MAPT protein, human; D008869:Microtubule-Associated Proteins; D016875:tau Proteins