Phosphorylation of the AMPA receptor GluR1 subunit is required for synaptic plasticity and retention of spatial memory

Hey-Kyoung Lee, Kogo Takamiya, Jung Soo Han, Hengye Man, Chong Hyun Kim, Gavin Rumbaugh, Sandy Yu, Lin Ding, Chun He, Ronald S. Petralia, Robert J. Wenthold, Michela Gallagher, Richard L Huganir

Research output: Contribution to journalArticle

Abstract

Plasticity of the nervous system is dependent on mechanisms that regulate the strength of synaptic transmission. Excitatory synapses in the brain undergo long-term potentiation (LTP) and long-term depression (LTD), cellular models of learning and memory. Protein phosphorylation is required for the induction of many forms of synaptic plasticity, including LTP and LTD. However, the critical kinase substrates that mediate plasticity have not been identified. We previously reported that phosphorylation of the GluR1 subunit of AMPA receptors, which mediate rapid excitatory transmission in the brain, is modulated during LTP and LTD. To test if GluR1 phosphorylation is necessary for plasticity and learning and memory, we generated mice with knockin mutations in the GluR1 phosphorylation sites. The phosphomutant mice show deficits in LTD and LTP and have memory defects in spatial learning tasks. These results demonstrate that phosphorylation of GluR1 is critical for LTD and LTP expression and the retention of memories.

Original languageEnglish (US)
Pages (from-to)631-643
Number of pages13
JournalCell
Volume112
Issue number5
DOIs
StatePublished - Mar 7 2003

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Phosphorylation
Neuronal Plasticity
Long-Term Potentiation
Plasticity
Depression
Data storage equipment
Brain
Learning
Neurology
Synaptic Transmission
Synapses
Nervous System
Phosphotransferases
AMPA 1 glutamate receptor ionotropic
Spatial Memory
Retention (Psychology)
Defects
Mutation
Substrates
Proteins

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Phosphorylation of the AMPA receptor GluR1 subunit is required for synaptic plasticity and retention of spatial memory. / Lee, Hey-Kyoung; Takamiya, Kogo; Han, Jung Soo; Man, Hengye; Kim, Chong Hyun; Rumbaugh, Gavin; Yu, Sandy; Ding, Lin; He, Chun; Petralia, Ronald S.; Wenthold, Robert J.; Gallagher, Michela; Huganir, Richard L.

In: Cell, Vol. 112, No. 5, 07.03.2003, p. 631-643.

Research output: Contribution to journalArticle

Lee, H-K, Takamiya, K, Han, JS, Man, H, Kim, CH, Rumbaugh, G, Yu, S, Ding, L, He, C, Petralia, RS, Wenthold, RJ, Gallagher, M & Huganir, RL 2003, 'Phosphorylation of the AMPA receptor GluR1 subunit is required for synaptic plasticity and retention of spatial memory', Cell, vol. 112, no. 5, pp. 631-643. https://doi.org/10.1016/S0092-8674(03)00122-3
Lee, Hey-Kyoung ; Takamiya, Kogo ; Han, Jung Soo ; Man, Hengye ; Kim, Chong Hyun ; Rumbaugh, Gavin ; Yu, Sandy ; Ding, Lin ; He, Chun ; Petralia, Ronald S. ; Wenthold, Robert J. ; Gallagher, Michela ; Huganir, Richard L. / Phosphorylation of the AMPA receptor GluR1 subunit is required for synaptic plasticity and retention of spatial memory. In: Cell. 2003 ; Vol. 112, No. 5. pp. 631-643.
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