Abstract
SummaryThe 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
AMPA-type glutamate receptors (AMPARs) initiate postsynaptic signaling at excitatory synapses (Traynelis et al, 2010; Trussell, 1999)
AMPAR mRNA Reprogramming after Activity Deprivation AMPAR i/o splicing is segregated in rodent hippocampus—flip isoforms dominate in CA3, whereas CA1 neurons express
Activity-Mediated AMPA Receptor Remodeling in CA1 i/o cassette is restricted to the CA1 subfield, i.e., is not apparent in CA3 (Figures 1B, S1B, and S1C) and is reversible—TTX washout reversed the processing pattern back to control (Figure S1F)
Summary
AMPA-type glutamate receptors (AMPARs) initiate postsynaptic signaling at excitatory synapses (Traynelis et al, 2010; Trussell, 1999). Receptor desensitization can shape synaptic transmission and in turn information processing (Chen et al, 2002; Koike-Tani et al, 2008; Rozov et al, 2001; Xu-Friedman and Regehr, 2003) as a function of the cleft glutamate transient (Cathala et al, 2005; Jonas, 2000; Xu-Friedman and Regehr, 2003). Neurons express a variety of functionally distinct AMPARs, which can be recruited selectively in response to different input patterns Activity-driven remodeling of kinetically distinct receptors would permit adaptive responses to changing input patterns
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