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

Penn, Andrew C, Balik, Ales, Wozny, Christian, Cais, Ondrej and Greger, Ingo H (2012) Activity-mediated AMPA receptor remodeling, driven by alternative splicing in the ligand-binding domain. Neuron, 76 (3). pp. 503-510. ISSN 0896-6273

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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.

Item Type: Article
Schools and Departments: School of Life Sciences > Neuroscience
Subjects: Q Science
Q Science > QH Natural history > QH0301 Biology
Q Science > QP Physiology > QP0351 Neurophysiology and neuropsychology
R Medicine > RC Internal medicine > RC0321 Neurosciences. Biological psychiatry. Neuropsychiatry
Depositing User: Andrew Penn
Date Deposited: 07 Oct 2015 09:28
Last Modified: 24 Mar 2017 14:47
URI: http://sro.sussex.ac.uk/id/eprint/57004

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