Cited by 235Neuroscience and Neuropharmacology ResearchReceptor Mechanisms and SignalingCellular transport and secretion

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Photoinactivation of Native AMPA Receptors Reveals Their Real-Time Trafficking

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Adesnik, Hillel, Nicoll, Roger A., England, Pamela M.·2005·Neuron

DOI 10.1016/j.neuron.2005.11.030

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Abstract

AMPA receptors mediate the majority of the fast excitatory transmission in the central nervous system. Much evidence suggests that the fast trafficking of AMPA receptors into and out of the postsynaptic membrane underlies changes in synaptic strength thought to be necessary for higher cognitive functions such as learning and memory. Despite the abundance of research conducted in this area, a direct, real-time functional assay that measures the trafficking of native AMPA receptors has been lacking. Toward this aim, we use a photoreactive, irreversible antagonist of AMPA receptors, ANQX, to rapidly silence surface AMPA receptors and investigate directly the trafficking of native AMPA receptors in real time. We find that the most dynamic movement of AMPA receptors occurs by lateral movement across the surface of neurons. Fast cycling of surface AMPA receptors with receptors from internal stores does occur but exclusively at extrasynaptic somatic sites. The cycling of synaptic AMPA receptors only occurs on a much longer timescale with complete exchange requiring at least 16 hr. This cycling is not dependent on protein synthesis or action potential driven network activity. These data suggest a revised model of AMPA receptor trafficking wherein a large internal store of AMPA receptors exchanges rapidly with extrasynaptic somatic AMPA receptors, and these newly inserted AMPA receptors then travel laterally along dendrites to reside stably at synapses.

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Authors: Adesnik, H., Nicoll, R. A., & England, P. M.
Affiliations: University of California, San Francisco (US)
Corresponding author: Nicoll, Roger A.
England, Pamela M.
ORCID: Adesnik, Hillel
Nicoll, Roger A.
England, Pamela M.
Venue: Neuron
Publisher: Elsevier BV
Published: 2005-12
Volume: 48
Issue: 6
Pages: 977-985
ISSN: 0896-6273 (ISSN-L)
DOI: 10.1016/j.neuron.2005.11.030
OpenAlex: W2161458381
Cited by: 234
References: 36
Citations by year: 2024: 2 · 2022: 1 · 2021: 5 · 2020: 4 · 2019: 7 · 2018: 7 · 2017: 5 · 2016: 4 · 2015: 9 · 2014: 14 · 2013: 12 · 2012: 16
FWCI: 10.97
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 2785 d)
Locations: Neuron (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
Keywords: AMPA receptors, receptor trafficking, photoinactivation, extrasynaptic receptors, synaptic plasticity, lateral diffusion, dendritic transport, excitatory synaptic transmission, learning and memory
MeSH terms: Animals, Animals, Newborn, Brain, Cell Membrane, Cells, Cultured, Dendrites, Endocytosis, Models, Neurological, Synaptic Transmission, Neurochemistry, Neurons, Nitro Compounds, Photochemistry, Quinolines, Time Factors, Rats, Sprague-Dawley, Receptors, AMPA, Excitatory Amino Acid Antagonists, Protein Transport, Rats

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Photoinactivation of Native AMPA Receptors Reveals Their Real-Time Trafficking

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