Hippocampal tauopathy in tau transgenic mice coincides with impaired hippocampus-dependent learning and memory, and attenuated late-phase long-term depression of synaptic transmission

Neurobiol Learn Mem. 2011 Mar;95(3):296-304. doi: 10.1016/j.nlm.2010.12.005. Epub 2010 Dec 16.


We evaluated various forms of hippocampus-dependent learning and memory, and hippocampal synaptic plasticity in THY-Tau22 transgenic mice, a murine tauopathy model that expresses double-mutated 4-repeat human tau, and shows neuropathological tau hyperphosphorylation and aggregation throughout the brain. Focussing on hippocampus, immunohistochemical studies in aged THY-Tau22 mice revealed prominent hyper- and abnormal phosphorylation of tau in CA1 region, and an increase in glial fibrillary acidic protein (GFAP) in hippocampus, but without signs of neuronal loss. These mice displayed spatial, social, and contextual learning and memory defects that could not be reduced to subtle neuromotor disability. The behavioral defects coincided with changes in hippocampal synaptic functioning and plasticity as measured in paired-pulse and novel long-term depression protocols. These results indicate that hippocampal tauopathy without neuronal cell loss can impair neural and behavioral plasticity, and further show that transgenic mice, such as the THY-Tau22 strain, might be useful for preclinical research on tauopathy pathogenesis and possible treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Association Learning / physiology*
  • Conditioning, Classical / physiology
  • Disease Models, Animal
  • Fear
  • Food Preferences
  • Hippocampus / metabolism
  • Hippocampus / pathology
  • Hippocampus / physiopathology*
  • Humans
  • Immunohistochemistry
  • Long-Term Synaptic Depression / physiology*
  • Male
  • Maze Learning / physiology*
  • Memory, Short-Term / physiology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Phosphorylation
  • Social Behavior
  • Tauopathies / metabolism
  • Tauopathies / pathology
  • Tauopathies / physiopathology*
  • tau Proteins / genetics
  • tau Proteins / metabolism


  • tau Proteins