Activity-mediated AMPA receptor remodeling, driven by alternative splicing in the ligand-binding domain

Andrew C Penn, Ales Balik, Christian Wozny, Ondrej Cais, Ingo H Greger

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

The AMPA-type glutamate receptor (AMPAR) subunit composition shapes synaptic transmission and varies throughout development and in response to different input patterns. Here, we show that chronic activity deprivation gives rise to synaptic AMPAR responses with enhanced fidelity. Extrasynaptic AMPARs exhibited changes in kinetics and pharmacology associated with splicing of the alternative flip/flop exons. AMPAR mRNA indeed exhibited reprogramming of the flip/flop exons for GluA1 and GluA2 subunits in response to activity, selectively in the CA1 subfield. However, the functional changes did not directly correlate with the mRNA expression profiles but result from altered assembly of GluA1/GluA2 subunit splice variants, uncovering an additional regulatory role for flip/flop splicing in excitatory signaling. Our results suggest that activity-dependent AMPAR remodeling underlies changes in short-term synaptic plasticity and provides a mechanism for neuronal homeostasis.

LanguageEnglish
Pages503-510
Number of pages8
JournalNeuron
Volume76
Issue number3
DOIs
Publication statusPublished - 8 Nov 2012

Fingerprint

AMPA Receptors
Glutamate Receptors
Alternative Splicing
Ligands
Exons
Messenger RNA
Neuronal Plasticity
Synaptic Transmission
Homeostasis
Pharmacology

Keywords

  • animals
  • animals, newborn
  • exons
  • hippocampus
  • ligands
  • organ culture techniques
  • protein binding
  • protein isoforms
  • protein structure, tertiary
  • rats
  • rats, sprague-dawley
  • receptors, AMPA

Cite this

Penn, Andrew C ; Balik, Ales ; Wozny, Christian ; Cais, Ondrej ; Greger, Ingo H. / Activity-mediated AMPA receptor remodeling, driven by alternative splicing in the ligand-binding domain. In: Neuron. 2012 ; Vol. 76, No. 3. pp. 503-510.
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abstract = "The AMPA-type glutamate receptor (AMPAR) subunit composition shapes synaptic transmission and varies throughout development and in response to different input patterns. Here, we show that chronic activity deprivation gives rise to synaptic AMPAR responses with enhanced fidelity. Extrasynaptic AMPARs exhibited changes in kinetics and pharmacology associated with splicing of the alternative flip/flop exons. AMPAR mRNA indeed exhibited reprogramming of the flip/flop exons for GluA1 and GluA2 subunits in response to activity, selectively in the CA1 subfield. However, the functional changes did not directly correlate with the mRNA expression profiles but result from altered assembly of GluA1/GluA2 subunit splice variants, uncovering an additional regulatory role for flip/flop splicing in excitatory signaling. Our results suggest that activity-dependent AMPAR remodeling underlies changes in short-term synaptic plasticity and provides a mechanism for neuronal homeostasis.",
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Activity-mediated AMPA receptor remodeling, driven by alternative splicing in the ligand-binding domain. / Penn, Andrew C; Balik, Ales; Wozny, Christian; Cais, Ondrej; Greger, Ingo H.

In: Neuron, Vol. 76, No. 3, 08.11.2012, p. 503-510.

Research output: Contribution to journalArticle

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AU - Penn, Andrew C

AU - Balik, Ales

AU - Wozny, Christian

AU - Cais, Ondrej

AU - Greger, Ingo H

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N2 - The AMPA-type glutamate receptor (AMPAR) subunit composition shapes synaptic transmission and varies throughout development and in response to different input patterns. Here, we show that chronic activity deprivation gives rise to synaptic AMPAR responses with enhanced fidelity. Extrasynaptic AMPARs exhibited changes in kinetics and pharmacology associated with splicing of the alternative flip/flop exons. AMPAR mRNA indeed exhibited reprogramming of the flip/flop exons for GluA1 and GluA2 subunits in response to activity, selectively in the CA1 subfield. However, the functional changes did not directly correlate with the mRNA expression profiles but result from altered assembly of GluA1/GluA2 subunit splice variants, uncovering an additional regulatory role for flip/flop splicing in excitatory signaling. Our results suggest that activity-dependent AMPAR remodeling underlies changes in short-term synaptic plasticity and provides a mechanism for neuronal homeostasis.

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KW - organ culture techniques

KW - protein binding

KW - protein isoforms

KW - protein structure, tertiary

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KW - rats, sprague-dawley

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