title: Mechanisms underlying the rapid induction and sustained expression of synaptic homeostasis.
abstract: Homeostatic signaling systems are thought to interface with the mechanisms of neural plasticity to achieve stable yet flexible neural circuitry. However, the time course, molecular design, and implementation of homeostatic signaling remain poorly defined. Here we demonstrate that a homeostatic increase in presynaptic neurotransmitter release can be induced within minutes following postsynaptic glutamate receptor blockade. The rapid induction of synaptic homeostasis is independent of new protein synthesis and does not require evoked neurotransmission, indicating that a change in the efficacy of spontaneous quantal release events is sufficient to trigger the induction of synaptic homeostasis. Finally, both the rapid induction and the sustained expression of synaptic homeostasis are blocked by mutations that disrupt the pore-forming subunit of the presynaptic Ca(V)2.1 calcium channel encoded by cacophony. These data confirm the presynaptic expression of synaptic homeostasis and implicate presynaptic Ca(V)2.1 in a homeostatic retrograde signaling system.
authors.affiliation: Department of Biochemistry and Biophysics, Neuroscience Program, University of California, San Francisco, 1550 4th Street, Rock Hall 4th Floor North, San Francisco, California 94158, USA.
authors.forename: C Andrew
authors.initials: CA
authors.lastname: Frank
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Kennedy
authors.forename: Carleton P
authors.initials: CP
authors.lastname: Goold
authors.forename: Kurt W
authors.initials: KW
authors.lastname: Marek
authors.forename: Graeme W
authors.initials: GW
authors.lastname: Davis
mesh_terms: D000818:Animals; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism*; D020864:Calcium Channels, N-Type / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D006706:Homeostasis / Q000235:genetics*; D008564:Membrane Potentials / Q000187:drug effects / Q000235:genetics; D009046:Motor Neurons / Q000187:drug effects / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D009469:Neuromuscular Junction / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D013570:Synaptic Membranes / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000235:genetics*; D013572:Synaptic Vesicles / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors
chemical_list: D015220:Calcium Channels; D020864:Calcium Channels, N-Type; D029721:Drosophila Proteins; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; C472405:cac protein, Drosophila; C104722:glutamate receptor ionotropic, AMPA 2