Synaptic activity regulates AMPA receptor trafficking through different recycling pathways

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Abstract

Changes in glutamatergic synaptic strength in brain are dependent on AMPA-type glutamate receptor (AMPAR) recycling, which is assumed to occur through a single local pathway. Here we present evidence that AMPAR recycling occurs through different pathways regulated by synaptic activity. Without synaptic stimulation, most AMPARs recycled in dynamin-independent endosomes containing the GTPase, Arf6. Few AMPARs recycled in dynamin-dependent endosomes labeled by transferrin receptors (TfRs). AMPAR recycling was blocked by alterations in the GTPase, TC10, which co-localized with Arf6 endosomes. TC10 mutants that reduced AMPAR recycling had no effect on increased AMPAR levels with long-term potentiation (LTP) and little effect on decreased AMPAR levels with long-term depression. However, internalized AMPAR levels in TfR-containing recycling endosomes increased after LTP, indicating increased AMPAR recycling through the dynamin-dependent pathway with synaptic plasticity. LTP-induced AMPAR endocytosis is inconsistent with local recycling as a source of increased surface receptors, suggesting AMPARs are trafficked from other sites.

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Ning Zheng

Department of Neurobiology, University of Chicago, Chicago, United States

Competing interests
The authors declare that no competing interests exist.
Okunola Jeyifous

Department of Neurobiology, University of Chicago, Chicago, United States

For correspondence
ojeyifou@bsd.uchicago.edu

Competing interests
The authors declare that no competing interests exist.
Charlotte Munro

Department of Physiology, University of Auckland, Auckland, New Zealand

Competing interests
The authors declare that no competing interests exist.
Johanna M Montgomery

Department of Physiology, University of Auckland, Auckland, New Zealand

Competing interests
The authors declare that no competing interests exist.
William N Green

Department of Neurobiology, University of Chicago, Chicago, United States

Competing interests
The authors declare that no competing interests exist.

Ethics

Animal experimentation: We followed AVMA guidelines to prevent pain and suffering of animals, and only used the minimum number of animals necessary to obtain conclusions in our experiments. Any pain, discomfort, or distress associated with the surgical procedures was prevented by the administration of the volatile anesthetic, Isoflurane. All animal procedures have been approved by the University of Chicago Institutional Animal Care and Use Committee (IACUC/ACUP protocol #72016) and are in accordance with the recommendations of the Panel on Euthanasia of the American Veterinary Medical Association.

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