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Cell Rep. 2018 Dec 26;25(13):3631-3646.e3. doi: 10.1016/j.celrep.2018.12.010.

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

Author information

1
Department 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.
2
Department of Brain and Cognitive Sciences, College of Natural Sciences, Seoul National University, Seoul 151-746, Korea; Neuroscience & Mental Health Program, The Hospital for Sick Children, Toronto, ON, Canada.
3
Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON M5G 1X5, Canada.
4
Neuroscience Research Institute, Seoul National University College of Medicine, 28 Yeongeon-dong, Jongno-gu, Seoul 110-799, Korea; Department of Physiology, Seoul National University College of Medicine, 28, Yeongeon-dong, Jongno-gu, Seoul 110-799, Korea.
5
School of Physiology, Pharmacology & Neuroscience, University of Bristol, Dorothy Hodgkin Building, Whitson Street, Bristol BS1 3NY, UK.
6
Department of Brain and Cognitive Sciences, College of Natural Sciences, Seoul National University, Seoul 151-746, Korea; School of Physiology, Pharmacology & Neuroscience, University of Bristol, Dorothy Hodgkin Building, Whitson Street, Bristol BS1 3NY, UK.
7
Department of Brain and Cognitive Sciences, DGIST, and Korea Brain Institute (KBRI), Daegu, 41068, Korea.
8
Department of Biomedical Sciences, Korea University College of Medicine, Seoul 136-705, Seoul, Korea.
9
Department of Brain and Cognitive Sciences, College of Natural Sciences, Seoul National University, Seoul 151-746, Korea; Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada; Department of Biological Sciences, College of Natural Sciences, Seoul National University, Building 504, Room 202, 599 Gwanangno, Gwanak-gu 151-747, Seoul, Korea; Center for Neuron and Disease, Frontier Institutes of Science and Technology, Xi'an Jiaotong University, Xi'an, 710049, China.
10
Department of Brain and Cognitive Sciences, College of Natural Sciences, Seoul National University, Seoul 151-746, Korea; Department of Biological Sciences, College of Natural Sciences, Seoul National University, Building 504, Room 202, 599 Gwanangno, Gwanak-gu 151-747, Seoul, Korea; Center for Neuron and Disease, Frontier Institutes of Science and Technology, Xi'an Jiaotong University, Xi'an, 710049, China.
11
Department 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; Department of Physiology, Seoul National University College of Medicine, 28, Yeongeon-dong, Jongno-gu, Seoul 110-799, Korea. Electronic address: sangjkim@snu.ac.kr.
12
Department of Brain and Cognitive Sciences, College of Natural Sciences, Seoul National University, Seoul 151-746, 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; Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada. Electronic address: collingridge@lunenfeld.ca.

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.

KEYWORDS:

AMPA; DHPG; FM dye; LTD; Long-term depression; P(r); mGluR; metabotropic; probability of release; theta burst

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