Surface Mobility of Postsynaptic AMPARs Tunes Synaptic Transmission

• Published in: Science (American Association for the Advancement of Science) Vol. 320; no. 5873; pp. 201 - 205
• Main Authors: Heine, Martin, Groc, Laurent, Frischknecht, Renato, Béïque, Jean-Claude, Lounis, Brahim, Rumbaugh, Gavin, Huganir, Richard L, Cognet, Laurent, Choquet, Daniel
• Format: Journal Article
• Language: English
• Published: Washington, DC American Association for the Advancement of Science 11.04.2008; The American Association for the Advancement of Science; American Association for the Advancement of Science (AAAS)
• Subjects: Action Potentials; Aminoacid receptors (glycine, glutamate, gaba); Animals; Antibodies; Biological and medical sciences; Brain; Brain research; Calcium; Calcium - metabolism; Cell receptors; Cell structures and functions; Cells, Cultured; Diffusion; Excitatory Amino Acid Antagonists - pharmacology; Excitatory Postsynaptic Potentials; Fluorescence; Fluorescence Recovery After Photobleaching; Fundamental and applied biological sciences. Psychology; Glutamic Acid - metabolism; Hippocampus - cytology; Hippocampus - physiology; Inurement; Kynurenic Acid - pharmacology; Molecular and cellular biology; Neuronal Plasticity; Neurons; Neurons - physiology; Neuroscience; Neurosciences; Patch-Clamp Techniques; Physiological regulation; Rats; Rats, Sprague-Dawley; Receptors; Receptors, AMPA - metabolism; Recombinant Fusion Proteins - metabolism; Synapses; Synapses - drug effects; Synapses - physiology; Synaptic transmission; Synaptic Transmission - drug effects; Transfection; Postsynaptic transmission; AMPA receptor; Desensitization; Synaptic transmission; Synaptic depression; Stimulation; Glutamate receptor; Postsynaptic density; In vitro; Recovery; Release; Biological receptor
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1152089

AMPA glutamate receptors (AMPARs) mediate fast excitatory synaptic transmission. Upon fast consecutive synaptic stimulation, transmission can be depressed. Recuperation from fast synaptic depression has been attributed solely to recovery of transmitter release and/or AMPAR desensitization. We show that AMPAR lateral diffusion, observed in both intact hippocampi and cultured neurons, allows fast exchange of desensitized receptors with naïve functional ones within or near the postsynaptic density. Recovery from depression in the tens of millisecond time range can be explained in part by this fast receptor exchange. Preventing AMPAR surface movements through cross-linking, endogenous clustering, or calcium rise all slow recovery from depression. Physiological regulation of postsynaptic receptor mobility affects the fidelity of synaptic transmission by shaping the frequency dependence of synaptic responses.