TY - JOUR
T1 - Accelerated extinction of conditioned taste aversion in P301L tau transgenic mice
AU - Pennanen, Luis
AU - Welzl, Hans
AU - D'Adamo, Patrizia
AU - Nitsch, Roger M.
AU - Götz, Jürgen
PY - 2004/4
Y1 - 2004/4
N2 - 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.
AB - 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.
KW - Alzheimer's disease
KW - Amygdala
KW - Conditioned taste aversion
KW - Extinction
KW - Frontotemporal dementia
KW - Neurofibrillary tangles
KW - Tau
KW - Transgenic mice
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UR - http://www.scopus.com/inward/citedby.url?scp=1842431831&partnerID=8YFLogxK
U2 - 10.1016/j.nbd.2003.11.020
DO - 10.1016/j.nbd.2003.11.020
M3 - Article
C2 - 15056457
AN - SCOPUS:1842431831
VL - 15
SP - 500
EP - 509
JO - Neurobiology of Disease
JF - Neurobiology of Disease
SN - 0969-9961
IS - 3
ER -