Microtubule-associated protein tau is essential for long-term depression in the hippocampus

Tetsuya Kimura, Daniel J Whitcomb, Jihoon Jo, Philip Regan, Thomas Piers, Seonghoo Heo, Christopher Brown, Tsutomu Hashikawa, Miyuki Murayama, Heon Seok, Ioannis Sotiropoulos, Eunjoon Kim, Graham L Collingridge, Akihiko Takashima, Kwangwook Cho

Research output: Contribution to journalArticlepeer-review

219 Citations (SciVal)


The microtubule-associated protein tau is a principal component of neurofibrillary tangles, and has been identified as a key molecule in Alzheimer's disease and other tauopathies. However, it is unknown how a protein that is primarily located in axons is involved in a disease that is believed to have a synaptic origin. To investigate a possible synaptic function of tau, we studied synaptic plasticity in the hippocampus and found a selective deficit in long-term depression (LTD) in tau knockout mice in vivo and in vitro, an effect that was replicated by RNAi knockdown of tau in vitro. We found that the induction of LTD is associated with the glycogen synthase kinase-3-mediated phosphorylation of tau. These observations demonstrate that tau has a critical physiological function in LTD.

Original languageEnglish
Article number20130144
JournalPhilosophical transactions of the Royal Society of London. Series B, Biological sciences
Issue number1633
Publication statusPublished - 5 Jan 2014


  • Animals
  • Blotting, Western
  • Glycogen Synthase Kinase 3/metabolism
  • Hippocampus/physiology
  • Immunohistochemistry
  • Long-Term Synaptic Depression/physiology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microdissection
  • Microscopy, Electron
  • Phosphorylation
  • RNA Interference
  • Rats
  • Rats, Wistar
  • Subcellular Fractions
  • Synapses/physiology
  • Tauopathies/physiopathology
  • tau Proteins/genetics


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