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

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posted on 2023-06-08, 22:41 authored by Andrew PennAndrew Penn, Ales Balik, Christian Wozny, Ondrej Cais, Ingo H Greger
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.

History

Publication status

  • Published

File Version

  • Published version

Journal

Neuron

ISSN

0896-6273

Publisher

Elsevier

Issue

3

Volume

76

Page range

503-510

Department affiliated with

  • Neuroscience Publications

Full text available

  • Yes

Peer reviewed?

  • Yes

Legacy Posted Date

2015-10-07

First Open Access (FOA) Date

2015-10-07

First Compliant Deposit (FCD) Date

2015-10-07

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