Cognition and hippocampal synaptic plasticity in mice with a homozygous tau deletion

Neurobiol Aging. 2014 Nov;35(11):2474-2478. doi: 10.1016/j.neurobiolaging.2014.05.005. Epub 2014 May 10.


Tau has been implicated in the organization, stabilization, and dynamics of microtubules. In Alzheimer's disease and more than 20 neurologic disorders tau missorting, hyperphosphorylation, and aggregation is a hallmark. They are collectively referred to as tauopathies. Although the impact of human tauopathies on cognitive processes has been explored in transgenic mouse models, the functional consequences of tau deletion on cognition are far less investigated. Here, we subjected tau knock-out (KO) mice to a battery of neurocognitive, behavioral, and electrophysiological tests. Although KO and wild-type mice were indistinguishable in motor abilities, exploratory and anxiety behavior, KO mice showed impaired contextual and cued fear conditioning. In contrast, extensive spatial learning in the water maze resulted in better performance of KO mice during acquisition. In electrophysiological experiments, basal synaptic transmission and paired-pulse facilitation in the hippocampal CA1-region were unchanged. Interestingly, deletion of tau resulted in severe deficits in long-term potentiation but not long-term depression. Our results suggest a role of tau in certain cognitive functions and implicate long-term potentiation as the relevant physiological substrate.

Keywords: Alzheimer's disease; Cognition; Hippocampus; Long-term depression; Morris water maze; Synaptic plasticity; Tau knock-out mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cognition*
  • Disease Models, Animal
  • Gene Deletion
  • Hippocampus / physiopathology*
  • Homozygote
  • Long-Term Potentiation
  • Male
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microtubules / metabolism
  • Neuronal Plasticity*
  • Spatial Learning
  • Synaptic Transmission
  • Tauopathies / physiopathology*
  • Tauopathies / psychology*
  • tau Proteins / physiology*


  • tau Proteins