Accelerated extinction of conditioned taste aversion in P301L tau transgenic mice

Neurobiol Dis. 2004 Apr;15(3):500-9. doi: 10.1016/j.nbd.2003.11.020.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anxiety
  • Behavior, Animal / physiology*
  • Brain / pathology*
  • Brain / physiology
  • Conditioning, Classical / physiology
  • Disease Models, Animal
  • Extinction, Psychological / physiology*
  • Humans
  • Immunohistochemistry
  • Mice
  • Mice, Transgenic
  • Microtubule-Associated Proteins / genetics*
  • Neurodegenerative Diseases / genetics
  • Neurofibrillary Tangles / pathology
  • Taste / physiology
  • tau Proteins / biosynthesis
  • tau Proteins / genetics*

Substances

  • MAPT protein, human
  • Microtubule-Associated Proteins
  • tau Proteins