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

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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  • Lateral diffusion of receptors through the plasma membrane and activity-triggered exocytosis of receptors from internal endosomal compartments are generally accepted regulation mechanisms for synaptic plasticity.

    “Lateral diffusion of receptors through the plasma membrane and activity-triggered exocytosis of receptors from internal endosomal compartments have become generally accepted regulation mechanisms for synaptic plasticity, although their respective contributions have remained unresolved”

    From Barriers in the brain: resolving dendritic spine morphology and compartmentalization (2014) · cites this paper as Adesnik et al., 2005

  • The respective contributions of lateral diffusion and activity-triggered exocytosis to synaptic plasticity remain unresolved.

    “although their respective contributions have remained unresolved (Passafaro et al., 2001; Borgdorff and Choquet, 2002; Adesnik et al., 2005; Ashby et al., 2006; Park et al., 2006; Ehlers et al., 2007; Heine et al., 2008; Newpher and Ehlers, 2008; Yang et al., 2008; Kennedy et al., 2010; Opazo and Choquet, 2011; Czöndör et al., 2012; Czöndör and Thoumine, 2013).”

    From Barriers in the brain: resolving dendritic spine morphology and compartmentalization (2014) · cites this paper as Adesnik et al., 2005

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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
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
Licence
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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