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Activity-mediated AMPA receptor remodeling, driven by alternative splicing in the ligand-binding domain
journal contribution
posted on 2023-06-08, 22:41 authored by Andrew PennAndrew Penn, Ales Balik, Christian Wozny, Ondrej Cais, Ingo H GregerThe 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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Publication status
- Published
File Version
- Published version
Journal
NeuronISSN
0896-6273Publisher
ElsevierExternal DOI
Issue
3Volume
76Page range
503-510Department affiliated with
- Neuroscience Publications
Full text available
- Yes
Peer reviewed?
- Yes
Legacy Posted Date
2015-10-07First Open Access (FOA) Date
2015-10-07First Compliant Deposit (FCD) Date
2015-10-07Usage metrics
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