Phosphorylation of ampa receptors is required for sensory deprivation-induced homeostatic synaptic plasticity

Anubhuti Goel, Linda W. Xu, Kevin P. Snyder, Lihua Song, Yamila Goenaga-Vazquez, Andrea Megill, Kogo Takamiya, Richard L. Huganir, Hey Kyoung Lee

Research output: Contribution to journalArticle

Abstract

Sensory experience, and the lack thereof, can alter the function of excitatory synapses in the primary sensory cortices. Recent evidence suggests that changes in sensory experience can regulate the synaptic level of Ca2+-permeable AMPA receptors (CP-AMPARs). However, the molecular mechanisms underlying such a process have not been determined. We found that binocular visual deprivation, which is a well-established in vivo model to produce multiplicative synaptic scaling in visual cortex of juvenile rodents, is accompanied by an increase in the phosphorylation of AMPAR GluR1 (or GluA1) subunit at the serine 845 (S845) site and the appearance of CP-AMPARs at synapses. To address the role of GluR1-S845 in visual deprivation-induced homeostatic synaptic plasticity, we used mice lacking key phosphorylation sites on the GluR1 subunit. We found that mice specifically lacking the GluR1-S845 site (GluR1-S845A mutants), which is a substrate of cAMP-dependent kinase (PKA), show abnormal basal excitatory synaptic transmission and lack visual deprivation-induced homeostatic synaptic plasticity. We also found evidence that increasing GluR1-S845 phosphorylation alone is not sufficient to produce normal multiplicative synaptic scaling. Our study provides concrete evidence that a GluR1 dependent mechanism, especially S845 phosphorylation, is a necessary pre-requisite step for in vivo homeostatic synaptic plasticity.

Original languageEnglish (US)
Article numbere18264
JournalPLoS One
Volume6
Issue number3
DOIs
StatePublished - 2011

Fingerprint

Sensory Deprivation
Phosphorylation
Neuronal Plasticity
serine
Serine
Plasticity
phosphorylation
receptors
AMPA Receptors
synapse
Synapses
calcium
synaptic transmission
Binoculars
mice
Visual Cortex
Synaptic Transmission
Rodentia
cortex
phosphotransferases (kinases)

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Phosphorylation of ampa receptors is required for sensory deprivation-induced homeostatic synaptic plasticity. / Goel, Anubhuti; Xu, Linda W.; Snyder, Kevin P.; Song, Lihua; Goenaga-Vazquez, Yamila; Megill, Andrea; Takamiya, Kogo; Huganir, Richard L.; Lee, Hey Kyoung.

In: PLoS One, Vol. 6, No. 3, e18264, 2011.

Research output: Contribution to journalArticle

Goel, Anubhuti ; Xu, Linda W. ; Snyder, Kevin P. ; Song, Lihua ; Goenaga-Vazquez, Yamila ; Megill, Andrea ; Takamiya, Kogo ; Huganir, Richard L. ; Lee, Hey Kyoung. / Phosphorylation of ampa receptors is required for sensory deprivation-induced homeostatic synaptic plasticity. In: PLoS One. 2011 ; Vol. 6, No. 3.
@article{df09c5d6153c47deb4c48c5405cf9771,
title = "Phosphorylation of ampa receptors is required for sensory deprivation-induced homeostatic synaptic plasticity",
abstract = "Sensory experience, and the lack thereof, can alter the function of excitatory synapses in the primary sensory cortices. Recent evidence suggests that changes in sensory experience can regulate the synaptic level of Ca2+-permeable AMPA receptors (CP-AMPARs). However, the molecular mechanisms underlying such a process have not been determined. We found that binocular visual deprivation, which is a well-established in vivo model to produce multiplicative synaptic scaling in visual cortex of juvenile rodents, is accompanied by an increase in the phosphorylation of AMPAR GluR1 (or GluA1) subunit at the serine 845 (S845) site and the appearance of CP-AMPARs at synapses. To address the role of GluR1-S845 in visual deprivation-induced homeostatic synaptic plasticity, we used mice lacking key phosphorylation sites on the GluR1 subunit. We found that mice specifically lacking the GluR1-S845 site (GluR1-S845A mutants), which is a substrate of cAMP-dependent kinase (PKA), show abnormal basal excitatory synaptic transmission and lack visual deprivation-induced homeostatic synaptic plasticity. We also found evidence that increasing GluR1-S845 phosphorylation alone is not sufficient to produce normal multiplicative synaptic scaling. Our study provides concrete evidence that a GluR1 dependent mechanism, especially S845 phosphorylation, is a necessary pre-requisite step for in vivo homeostatic synaptic plasticity.",
author = "Anubhuti Goel and Xu, {Linda W.} and Snyder, {Kevin P.} and Lihua Song and Yamila Goenaga-Vazquez and Andrea Megill and Kogo Takamiya and Huganir, {Richard L.} and Lee, {Hey Kyoung}",
year = "2011",
doi = "10.1371/journal.pone.0018264",
language = "English (US)",
volume = "6",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "3",

}

TY - JOUR

T1 - Phosphorylation of ampa receptors is required for sensory deprivation-induced homeostatic synaptic plasticity

AU - Goel, Anubhuti

AU - Xu, Linda W.

AU - Snyder, Kevin P.

AU - Song, Lihua

AU - Goenaga-Vazquez, Yamila

AU - Megill, Andrea

AU - Takamiya, Kogo

AU - Huganir, Richard L.

AU - Lee, Hey Kyoung

PY - 2011

Y1 - 2011

N2 - Sensory experience, and the lack thereof, can alter the function of excitatory synapses in the primary sensory cortices. Recent evidence suggests that changes in sensory experience can regulate the synaptic level of Ca2+-permeable AMPA receptors (CP-AMPARs). However, the molecular mechanisms underlying such a process have not been determined. We found that binocular visual deprivation, which is a well-established in vivo model to produce multiplicative synaptic scaling in visual cortex of juvenile rodents, is accompanied by an increase in the phosphorylation of AMPAR GluR1 (or GluA1) subunit at the serine 845 (S845) site and the appearance of CP-AMPARs at synapses. To address the role of GluR1-S845 in visual deprivation-induced homeostatic synaptic plasticity, we used mice lacking key phosphorylation sites on the GluR1 subunit. We found that mice specifically lacking the GluR1-S845 site (GluR1-S845A mutants), which is a substrate of cAMP-dependent kinase (PKA), show abnormal basal excitatory synaptic transmission and lack visual deprivation-induced homeostatic synaptic plasticity. We also found evidence that increasing GluR1-S845 phosphorylation alone is not sufficient to produce normal multiplicative synaptic scaling. Our study provides concrete evidence that a GluR1 dependent mechanism, especially S845 phosphorylation, is a necessary pre-requisite step for in vivo homeostatic synaptic plasticity.

AB - Sensory experience, and the lack thereof, can alter the function of excitatory synapses in the primary sensory cortices. Recent evidence suggests that changes in sensory experience can regulate the synaptic level of Ca2+-permeable AMPA receptors (CP-AMPARs). However, the molecular mechanisms underlying such a process have not been determined. We found that binocular visual deprivation, which is a well-established in vivo model to produce multiplicative synaptic scaling in visual cortex of juvenile rodents, is accompanied by an increase in the phosphorylation of AMPAR GluR1 (or GluA1) subunit at the serine 845 (S845) site and the appearance of CP-AMPARs at synapses. To address the role of GluR1-S845 in visual deprivation-induced homeostatic synaptic plasticity, we used mice lacking key phosphorylation sites on the GluR1 subunit. We found that mice specifically lacking the GluR1-S845 site (GluR1-S845A mutants), which is a substrate of cAMP-dependent kinase (PKA), show abnormal basal excitatory synaptic transmission and lack visual deprivation-induced homeostatic synaptic plasticity. We also found evidence that increasing GluR1-S845 phosphorylation alone is not sufficient to produce normal multiplicative synaptic scaling. Our study provides concrete evidence that a GluR1 dependent mechanism, especially S845 phosphorylation, is a necessary pre-requisite step for in vivo homeostatic synaptic plasticity.

UR - http://www.scopus.com/inward/record.url?scp=79953645899&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79953645899&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0018264

DO - 10.1371/journal.pone.0018264

M3 - Article

VL - 6

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 3

M1 - e18264

ER -