Diffusional trapping of GluR1 AMPA receptors by input-specific synaptic activity.
Synaptic activity regulates the postsynaptic accumulation of AMPA receptors over timescales ranging from minutes to days. Indeed, the regulated trafficking and mobility of GluR1 AMPA receptors underlies many forms of synaptic potentiation at glutamatergic synapses throughout the brain. However, the basis for synapse-specific accumulation of GluR1 is unknown. Here we report that synaptic activity locally immobilizes GluR1 AMPA receptors at individual synapses. Using single-molecule tracking together with the silencing of individual presynaptic boutons, we demonstrate that local synaptic activity reduces diffusional exchange of GluR1 between synaptic and extraynaptic domains, resulting in postsynaptic accumulation of GluR1. At neighboring inactive synapses, GluR1 is highly mobile with individual receptors frequently escaping the synapse. Within the synapse, spontaneous activity confines the diffusional movement of GluR1 to restricted subregions of the postsynaptic membrane. Thus, local activity restricts GluR1 mobility on a submicron scale, defining an input-specific mechanism for regulating AMPA receptor composition and abundance.
Ehlers
Michael D
MD
Department of Neurobiology, Howard Hughes Medical Institute, Duke University Medical Center, Durham, NC 27710, USA. ehlers@neuro.duke.edu
Heine
Martin
M
Groc
Laurent
L
Lee
Ming-Chia
MC
Choquet
Daniel
D
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D004622:Embryo, Mammalian; D049452:Green Fluorescent Proteins / Q000096:biosynthesis; D006624:Hippocampus; D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000502:physiology; D018408:Patch-Clamp Techniques; D021381:Protein Transport / Q000502:physiology; D051381:Rats; D013569:Synapses / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology*; D013997:Time Factors; D014161:Transduction, Genetic / Q000379:methods
D002352:Carrier Proteins; C491308:Grip1 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D049452:Green Fluorescent Proteins