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

Research output: Contribution to journalArticle

61 Citations (Scopus)

Abstract

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
Volume35
Issue number12
DOIs
Publication statusPublished - 25 Mar 2015

Keywords

  • 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

Cite this

Tau phosphorylation at serine 396 residue is required for hippocampal LTD. / Regan, Philip; Piers, Thomas; Yi, Jee-Hyun; Kim, Dong-Hyun; Huh, Seonghoo; Park, Se Jin; Ryu, Jong Hoon; Whitcomb, Daniel J; Cho, Kwangwook.

In: Journal of Neuroscience, Vol. 35, No. 12, 25.03.2015, p. 4804-4812.

Research output: Contribution to journalArticle

Regan, P, Piers, T, Yi, J-H, Kim, D-H, Huh, S, Park, SJ, Ryu, JH, Whitcomb, DJ & Cho, K 2015, 'Tau phosphorylation at serine 396 residue is required for hippocampal LTD', Journal of Neuroscience, vol. 35, no. 12, pp. 4804-4812. https://doi.org/10.1523/JNEUROSCI.2842-14.2015
Regan, Philip ; Piers, Thomas ; Yi, Jee-Hyun ; Kim, Dong-Hyun ; Huh, Seonghoo ; Park, Se Jin ; Ryu, Jong Hoon ; Whitcomb, Daniel J ; Cho, Kwangwook. / Tau phosphorylation at serine 396 residue is required for hippocampal LTD. In: Journal of Neuroscience. 2015 ; Vol. 35, No. 12. pp. 4804-4812.
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abstract = "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.",
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AU - Regan, Philip

AU - Piers, Thomas

AU - Yi, Jee-Hyun

AU - Kim, Dong-Hyun

AU - Huh, Seonghoo

AU - Park, Se Jin

AU - Ryu, Jong Hoon

AU - Whitcomb, Daniel J

AU - Cho, Kwangwook

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AB - 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.

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KW - Long-Term Potentiation/physiology

KW - Long-Term Synaptic Depression/physiology

KW - Male

KW - Mice

KW - Mice, Knockout

KW - Phosphorylation

KW - Rats

KW - Receptors, AMPA/metabolism

KW - Reversal Learning/physiology

KW - Serine/metabolism

KW - tau Proteins/genetics

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