title: Accelerated extinction of conditioned taste aversion in P301L tau transgenic mice.
abstract: 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.
authors.affiliation: Division of Psychiatry Research, University of Zürich, 8008 Zürich, Switzerland.
authors.forename: Luis
authors.initials: L
authors.lastname: Pennanen
authors.forename: Hans
authors.initials: H
authors.lastname: Welzl
authors.forename: Patrizia
authors.initials: P
authors.lastname: D'Adamo
authors.forename: Roger M
authors.initials: RM
authors.lastname: Nitsch
authors.forename: Jürgen
authors.initials: J
authors.lastname: Götz
mesh_terms: 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*
chemical_list: C054369:MAPT protein, human; D008869:Microtubule-Associated Proteins; D016875:tau Proteins