The Probability of Neurotransmitter Release Governs AMPA Receptor Trafficking via Activity-Dependent Regulation of mGluR1 Surface Expression

Thomas M Sanderson, Clarrisa A Bradley, John Georgiou, Yun Hwa Hong, Ai Na Ng, Yeseul Lee, Hee-Dae Kim, Doyeon Kim, Mascia Amici, Gi Hoon Son, Min Zhuo, Kyungjin Kim, Bong-Kiun Kaang, Sang Jeong Kim, Graham L Collingridge

Research output: Contribution to journalArticle (Academic Journal)

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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.

Original languageEnglish
Pages (from-to)3631-3646.e3
Number of pages20
JournalCell Reports
Volume25
Issue number13
Early online date26 Dec 2018
DOIs
Publication statusE-pub ahead of print - 26 Dec 2018

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  • Cite this

    Sanderson, T. M., Bradley, C. A., Georgiou, J., Hong, Y. H., Ng, A. N., Lee, Y., Kim, H-D., Kim, D., Amici, M., Son, G. H., Zhuo, M., Kim, K., Kaang, B-K., Kim, S. J., & Collingridge, G. L. (2018). The Probability of Neurotransmitter Release Governs AMPA Receptor Trafficking via Activity-Dependent Regulation of mGluR1 Surface Expression. Cell Reports, 25(13), 3631-3646.e3. https://doi.org/10.1016/j.celrep.2018.12.010