Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 107, Issue 50, Pages 21806-21811Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1016399107
Keywords
homeostasis; synaptic scaling; calcium signaling; miniature excitatory postsynaptic currents
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Funding
- National Institute of Mental Health
- National Institute of General Medical Sciences
- National Institute of Neurological Disorders and Stroke
- Wenner-Gren Foundation
- Helen Hay Whitney Foundation
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Prolonged blockade of AMPA-type glutamate receptors in hippocampal neuron cultures leads to homeostatic enhancements of pre- and postsynaptic function that appear correlated at individual synapses, suggesting some form of transsynaptic coordination. The respective modifications are important for overall synaptic strength but their interrelationship, dynamics, and molecular underpinnings are unclear. Here we demonstrate that adaptation begins postsynaptically but is ultimately communicated to presynaptic terminals and expressed as an accelerated turnover of synaptic vesicles. Critical postsynaptic modifications occur over hours, but enable retrograde communication within minutes once AMPA receptor (AMPAR) blockade is removed, causing elevation of both spontaneous and evoked vesicle fusion. The retrograde signaling does not require spiking activity and can be interrupted by NBQX, philanthotoxin, postsynaptic BAPTA, or external sequestration of BDNF, consistent with the acute release of retrograde messenger, triggered by postsynaptic Ca2+ elevation via Ca2+-permeable AMPARs.
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