title: Presynaptic effectors contributing to cAMP-induced synaptic potentiation in Drosophila.
abstract: cAMP analogs and activation of adenylyl cyclase by forskolin strongly potentiate synaptic transmission at the Drosophila neuromuscular junction. These effects are generally attributed to activation of cAMP-dependent protein kinase. Recent reports on crustacean and mammalian synapses have implicated other cAMP-dependent effectors in synaptic potentiation. Drosophila neuromuscular junctions were tested for effects of two known cAMP-dependent effectors: hyperpolarization-activated, cyclic nucleotide-regulated channels (HCNCs) and guanine nucleotide exchange protein activated by cAMP (Epac). Forskolin-induced enhancement of synaptic transmission was drastically reduced by a blocker of HCNCs, but not completely eliminated. A specific agonist for Epac modestly enhanced synaptic potentials. This agonist also stabilized their amplitudes in the presence of a blocker of HCNCs. The observations implicate HCNCs and Epac in cAMP-dependent potentiation that does not require cAMP-dependent protein kinase, indicating that additional previously unexplored factors contribute to synaptic plasticity in Drosophila. Genetic and molecular techniques available for Drosophila can be used to define the underlying molecular basis for cAMP-dependent synaptic potentiation.
authors.affiliation: Department of Physiology, University of Toronto, Faculty of Medicine, Toronto, Ontario, Canada M5S 1A8.
authors.forename: U
authors.initials: U
authors.lastname: Cheung
authors.forename: H L
authors.initials: HL
authors.lastname: Atwood
authors.forename: R S
authors.initials: RS
authors.lastname: Zucker
mesh_terms: D000818:Animals; D020126:Brefeldin A / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D054815:Cyclic Nucleotide-Gated Cation Channels; D004330:Drosophila; D020662:Guanine Nucleotide Exchange Factors / Q000819:agonists; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D007473:Ion Channels / Q000037:antagonists & inhibitors; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D009469:Neuromuscular Junction / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D015221:Potassium Channels; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D054815:Cyclic Nucleotide-Gated Cation Channels; C482601:Epac protein, mouse; D020662:Guanine Nucleotide Exchange Factors; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D007473:Ion Channels; D015221:Potassium Channels; D011500:Protein Synthesis Inhibitors; D005576:Colforsin; D020126:Brefeldin A; C053907:8-cyclopentyl-1,3-dimethylxanthine; D013806:Theophylline; D000242:Cyclic AMP