Linking Nanoscale Dynamics of AMPA Receptor Organization to Plasticity of Excitatory Synapses and Learning

被引:92
作者
Choquet, Daniel [1 ,2 ,3 ]
机构
[1] CNRS, Interdisciplinary Inst Neurosci, Unite Mixte Rech 5297, F-33000 Bordeaux, France
[2] Univ Bordeaux, Interdisciplinary Inst Neurosci, Unite Mixte Rech 5297, F-33000 Bordeaux, France
[3] Univ Bordeaux, UMS 3420, Bordeaux Imaging Ctr, US4 INSERM,CNRS, F-33000 Bordeaux, France
关键词
Synaptic plasticity; AMPA receptors; receptor trafficking; super resolution imaging; Long Term Potentiation; neurodegen-erative diseases; LONG-TERM POTENTIATION; BIDIRECTIONAL SYNAPTIC PLASTICITY; POSTSYNAPTIC DENSITY PROTEIN; OPTICAL QUANTAL ANALYSIS; GLUTAMATE RECEPTORS; HIPPOCAMPAL-NEURONS; DENDRITIC SPINES; SURFACE TRAFFICKING; GLYCINE RECEPTORS; GLUR1; SUBUNIT;
D O I
10.1523/JNEUROSCI.2119-18.2018
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
The spatiotemporal organization of neurotransmitter receptors in the postsynaptic membrane is a fundamental determinant of synaptic transmission and thus of information processing by the brain. The ionotropic AMPA subtype of glutamate receptors (AMPARs) mediate fast excitatory synaptic transmission in the CNS. The number of AMPARs located en face presynaptic glutamate release sites sets the efficacy of synaptic transmission. Understanding how this number is set and regulated has been the topic of intense research in the last two decades. We showed that AMPARs are not stable in the synapse as initially thought. They continuously enter and exit the postsynaptic density by lateral diffusion, and they exchange between the neuronal surface and intracellular compartments by endocytosis and exocytosis at extrasynaptic sites. Regulation of these various trafficking pathways has emerged as a key mechanism for activity-dependent plasticity of synaptic transmission, a process important for learning and memory. I here present my view of these findings. In particular, the advent of super-resolution microscopy and single-molecule tracking has helped to uncover the intricacy of AMPARs' dynamic organization at the nanoscale. In addition, AMPAR surface diffusion is highly regulated by a variety of factors, including neuronal activity, stress hormones, and neurodegeneration, suggesting that AMPAR diffusion-trapping may play a central role in synapse function. Using innovative tools to understand further the link between receptor dynamics and synapse plasticity is now unveiling new molecular mechanisms of learning. Modifying AMPAR dynamics may emerge as a new target to correct synapse dysfunction in the diseased brain.
引用
收藏
页码:9318 / 9329
页数:12
相关论文
共 169 条
[1]   Postsynaptic Complexin Controls AMPA Receptor Exocytosis during LTP [J].
Ahmad, Mohiuddin ;
Polepalli, Jai S. ;
Goswami, Debanjan ;
Yang, Xiaofei ;
Kaeser-Woo, Yea Jin ;
Suedhof, Thomas C. ;
Malenka, Robert C. .
NEURON, 2012, 73 (02) :260-267
[2]   Impaired regulation of synaptic strength in hippocampal neurons from GluR1-deficient mice [J].
Andrásfalvy, BK ;
Smith, MA ;
Borchardt, T ;
Sprengel, R ;
Magee, JC .
JOURNAL OF PHYSIOLOGY-LONDON, 2003, 552 (01) :35-45
[3]   Rapid Dispersion of SynGAP from Synaptic Spines Triggers AMPA Receptor Insertion and Spine Enlargement during LTP [J].
Araki, Yoichi ;
Zeng, Menglong ;
Zhang, Mingjie ;
Huganir, Richard L. .
NEURON, 2015, 85 (01) :173-189
[4]   Removal of AMPA receptors (AMPARs) from synapses is preceded by transient endocytosis of extrasynaptic AMPARs [J].
Ashby, MC ;
De La Rue, SA ;
Ralph, GS ;
Uney, J ;
Collingridge, GL ;
Henley, JM .
JOURNAL OF NEUROSCIENCE, 2004, 24 (22) :5172-5176
[5]   Lateral diffusion drives constitutive exchange of AMPA receptors at dendritic spines and is regulated by spine morphology [J].
Ashby, Michael C. ;
Maier, Susie R. ;
Nishimune, Atsushi ;
Henley, Jeremy M. .
JOURNAL OF NEUROSCIENCE, 2006, 26 (26) :7046-7055
[6]   LATERAL MOTION OF FLUORESCENTLY LABELED ACETYLCHOLINE RECEPTORS IN MEMBRANES OF DEVELOPING MUSCLE-FIBERS [J].
AXELROD, D ;
RAVDIN, P ;
KOPPEL, DE ;
SCHLESSINGER, J ;
WEBB, WW ;
ELSON, EL ;
PODLESKI, TR .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1976, 73 (12) :4594-4598
[7]   Regulatory phosphorylation of AMPA-type glutamate receptors by CaM-KII during long-term potentiation [J].
Barria, A ;
Muller, D ;
Derkach, V ;
Griffith, LC ;
Soderling, TR .
SCIENCE, 1997, 276 (5321) :2042-2045
[8]   The interaction between stargazin and PSD-95 regulates AMPA receptor surface trafficking [J].
Bats, Cecile ;
Groc, Laurent ;
Choquet, Daniel .
NEURON, 2007, 53 (05) :719-734
[9]   HIGH-RESOLUTION IMMUNOGOLD LOCALIZATION OF AMPA TYPE GLUTAMATE-RECEPTOR SUBUNITS AT SYNAPTIC AND NONSYNAPTIC SITES IN RAT HIPPOCAMPUS [J].
BAUDE, A ;
NUSSER, Z ;
MOLNAR, E ;
MCILHINNEY, RAJ ;
SOMOGYI, P .
NEUROSCIENCE, 1995, 69 (04) :1031-1055
[10]   Regulation of AMPA receptor endocytosis by a signaling mechanism shared with LTD [J].
Beattie, EC ;
Carroll, RC ;
Yu, X ;
Morishita, W ;
Yasuda, H ;
von Zastrow, M ;
Malenka, RC .
NATURE NEUROSCIENCE, 2000, 3 (12) :1291-1300