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Updated: Jan 31, 2026

A High-content Assay for Monitoring AMPA Receptor Trafficking
Published on: January 28, 2019
The Probability of Neurotransmitter Release Governs AMPA Receptor Trafficking via Activity-Dependent Regulation of
Thomas M Sanderson1, Clarrisa A Bradley2, John Georgiou3
1Department of Brain and Cognitive Sciences, College of Natural Sciences, Seoul National University, Seoul 151-746, Korea; Neuroscience Research Institute, Seoul National University College of Medicine, 28 Yeongeon-dong, Jongno-gu, Seoul 110-799, Korea; School of Physiology, Pharmacology & Neuroscience, University of Bristol, Dorothy Hodgkin Building, Whitson Street, Bristol BS1 3NY, UK; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON M5G 1X5, Canada.
Abstract:
A major mechanism contributing to synaptic plasticity involves alterations in the number of AMPA receptors (AMPARs) expressed at synapses. Hippocampal CA1 synapses, where this process has been most extensively studied, are highly heterogeneous with respect to their probability of neurotransmitter release, P(r). It is unknown whether there is any relationship between the extent of plasticity-related AMPAR trafficking and the initial P(r) of a synapse. To address this question, we induced metabotropic glutamate receptor (mGluR) dependent long-term depression (mGluR-LTD) and assessed AMPAR trafficking and P(r) at individual synapses, using SEP-GluA2 and FM4-64, respectively. We found that either pharmacological or synaptic activation of mGluR1 reduced synaptic SEP-GluA2 in a manner that depends upon P(r); this process involved an activity-dependent reduction in surface mGluR1 that selectively protects high-P(r) synapses from synaptic weakening. Consequently, the extent of postsynaptic plasticity can be pre-tuned by presynaptic activity.
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