Tau phosphorylation at serine 396 residue is required for hippocampal LTD

Philip Regan, Thomas Piers, Jee-Hyun Yi, Dong-Hyun Kim, Seonghoo Huh, Se Jin Park, Jong Hoon Ryu, Daniel J Whitcomb, Kwangwook Cho

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153 Citations (SciVal)


Tau is required for the induction of long-term depression (LTD) of synaptic transmission in the hippocampus. Here we probe the role of tau in LTD, finding that an AMPA receptor internalization mechanism is impaired in tau KO mice, and that LTD causes specific phosphorylation at the serine 396 and 404 residues of tau. Surprisingly, we find that phosphorylation at serine 396, specifically, is critical for LTD but has no role in LTP. Finally, we show that tau KO mice exhibit deficits in spatial reversal learning. These findings underscore the physiological role for tau at the synapse and identify a behavioral correlate of its role in LTD.

Original languageEnglish
Pages (from-to)4804-4812
Number of pages9
JournalJournal of Neuroscience
Issue number12
Publication statusPublished - 25 Mar 2015

Bibliographical note

Copyright © 2015 the authors 0270-6474/15/354804-09$15.00/0.


  • Animals
  • Endocytosis/physiology
  • Hippocampus/physiology
  • Long-Term Potentiation/physiology
  • Long-Term Synaptic Depression/physiology
  • Male
  • Mice
  • Mice, Knockout
  • Phosphorylation
  • Rats
  • Receptors, AMPA/metabolism
  • Reversal Learning/physiology
  • Serine/metabolism
  • tau Proteins/genetics


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