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Specific Roles of AMPA Receptor Subunit GluR1 (GluA1) Phosphorylation Sites in Regulating Synaptic Plasticity in the CA1 Region of Hippocampus

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Lee, Hey-Kyoung, Takamiya, Kogo, He, Kaiwen, Song, Lihua, Huganir, Richard L.·2010·Journal of Neurophysiology

DOI 10.1152/jn.00835.2009PMC PMC2807233

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Abstract

Activity-dependent changes in excitatory synaptic transmission in the CNS have been shown to depend on the regulation of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPARs). In particular, several lines of evidence suggest that reversible phosphorylation of AMPAR subunit glutamate receptor 1 (GluR1, also referred to as GluA1 or GluR-A) plays a role in long-term potentiation (LTP) and long-term depression (LTD). We previously reported that regulation of serines (S) 831 and 845 on the GluR1 subunit may play a critical role in bidirectional synaptic plasticity in the Schaffer collateral inputs to CA1. Specifically, gene knockin mice lacking both S831 and S845 phosphorylation sites ("double phosphomutants"), where both serine residues were replaced by alanines (A), showed a faster decaying LTP and a deficit in LTD. To determine which of the two phosphorylation sites was responsible for the phenotype, we have now generated two lines of gene knockin mice: one that specifically lacks S831 (S831A mutants) and another that lacks only S845 (S845A mutants). We found that S831A mutants display normal LTP and LTD, whereas S845A mutants show a specific deficit in LTD. Taken together with our previous results from the "double phosphomutants," our data suggest that either S831 or S845 alone may support LTP, whereas the S845 site is critical for LTD expression.

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Authors: Lee, H.-K., Takamiya, K., He, K., Song, L., & Huganir, R. L.
Affiliations: Howard Hughes Medical Institute (US)
University of Maryland, College Park (US)
Corresponding author: Huganir, Richard L.
ORCID: Lee, Hey-Kyoung
Takamiya, Kogo
He, Kaiwen
Huganir, Richard L.
Venue: Journal of Neurophysiology
Publisher: American Physiological Society
Published: 2010-01
Volume: 103
Issue: 1
Pages: 479-489
ISSN: 0022-3077 (ISSN-L)
1522-1598
DOI: 10.1152/jn.00835.2009
PMC: PMC2807233
OpenAlex: W2162552344
Cited by: 261
References: 65
Citations by year: 2026: 6 · 2025: 9 · 2024: 13 · 2023: 13 · 2022: 17 · 2021: 14 · 2020: 18 · 2019: 17 · 2018: 18 · 2017: 11 · 2016: 24 · 2015: 22 · 2014: 19 · 2013: 23 · 2012: 13
FWCI: 5.13
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Journal of Neurophysiology (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: Howard Hughes Medical Institute
National Eye Institute (R01EY014882)
National Institute of Neurological Disorders and Stroke (R01NS036715)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
Keywords: GluR1, AMPA receptors, GluR1 phosphorylation, long-term potentiation, long-term depression, bidirectional synaptic plasticity, hippocampal CA1, Schaffer collaterals, excitatory synaptic transmission
MeSH terms: Aging, Amino Acid Sequence, Animals, Base Sequence, Male, Mice, Inbred C57BL, Mice, Transgenic, Molecular Sequence Data, Mutation, Synaptic Transmission, Neurons, Phosphorylation, Synapses, Long-Term Potentiation, Receptors, AMPA, Long-Term Synaptic Depression, Mice, Gene Knock-In Techniques, CA1 Region, Hippocampal, In Vitro Techniques

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Specific Roles of AMPA Receptor Subunit GluR1 (GluA1) Phosphorylation Sites in Regulating Synaptic Plasticity in the CA1 Region of Hippocampus

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