Neuron
Volume 76, Issue 3, 8 November 2012, Pages 503-510
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Activity-Mediated AMPA Receptor Remodeling, Driven by Alternative Splicing in the Ligand-Binding Domain

https://doi.org/10.1016/j.neuron.2012.08.010Get rights and content
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Summary

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.

Highlights

► Homeostatic mechanism intrinsic to the AMPA receptor ► Circuitry-selective activity-driven alternative AMPA receptor splicing ► Neuronal homeostasis via AMPA receptor short-term plasticity in CA1 ► Functional capacity for flip/flop splicing in excitatory signaling

Cited by (0)

2

Present address: Université de Bordeaux, Interdisciplinary Institute for Neuroscience and CNRS, Interdisciplinary Institute for Neuroscience, UMR 5297, F-33000 Bordeaux, France

3

Present address: Institute of Physiology, Academy of Sciences of the Czech Republic v.v.i., Videnska 1083, 142 20 Prague 4, Czech Republic

4

Present address: Neuroscience Research Center, Charité – Universitätsmedizin Berlin, 10117 Berlin, Germany

5

These authors contributed equally to this work