title: Postsynaptic GluA1 enables acute retrograde enhancement of presynaptic function to coordinate adaptation to synaptic inactivity.
abstract: 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 Ca(2+) elevation via Ca(2+)-permeable AMPARs.
authors.affiliation: Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Lindskog
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Rachel D
authors.initials: RD
authors.lastname: Groth
authors.forename: Damon
authors.initials: D
authors.lastname: Poburko
authors.forename: Tara C
authors.initials: TC
authors.lastname: Thiagarajan
authors.forename: Xue
authors.initials: X
authors.lastname: Han
authors.forename: Richard W
authors.initials: RW
authors.lastname: Tsien
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002478:Cells, Cultured; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D006706:Homeostasis / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D018408:Patch-Clamp Techniques; D017729:Presynaptic Terminals / Q000378:metabolism*; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D013569:Synapses / Q000378:metabolism*; D013572:Synaptic Vesicles / Q000378:metabolism
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D018091:Receptors, AMPA; D009569:Nitric Oxide