title: The role of extracellular adenosine in regulating mossy fiber synaptic plasticity.
abstract: Hippocampal mossy fiber synapses show unique molecular features and dynamic range of plasticity. A recent paper proposed that the defining features of mossy fiber synaptic plasticity are caused by a local buildup of extracellular adenosine (Moore et al., 2003). In this study, we reassessed the role of ambient adenosine in regulating mossy fiber synaptic plasticity in mouse and rat hippocampal slices. Synaptic transmission was highly sensitive to activation of presynaptic adenosine A1 receptors (A1Rs), which reduced transmitter release by >75%. However, most of A1Rs were not activated by ambient adenosine. Field potentials increased only by 20-30% when A1Rs were fully blocked with the A1R antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) (1 microM). Moreover, blocking A1Rs hardly altered paired-pulse facilitation, frequency facilitation, or posttetanic potentiation. Frequency facilitation was similar in A1R-/- mice and when measured with NMDA receptor-mediated EPSCs in CA3 pyramidal cells in the presence of DPCPX. Additional experiments suggested that the results obtained by Moore et al. (2003) can partially be explained by their usage of a submerged recording chamber and elevated divalent cation concentrations. In conclusion, a reduction of the basal release probability by ambient adenosine does not underlie presynaptic forms of plasticity at mossy fiber synapses.
authors.affiliation: Department of Neurosurgery, University Clinic Bonn, D-53105 Bonn, Germany.
authors.forename: Maria
authors.initials: M
authors.lastname: Kukley
authors.forename: Maximilian
authors.initials: M
authors.lastname: Schwan
authors.forename: Bertil B
authors.initials: BB
authors.lastname: Fredholm
authors.forename: Dirk
authors.initials: D
authors.lastname: Dietrich
mesh_terms: D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000241:Adenosine / Q000031:analogs & derivatives / Q000502:physiology*; D058916:Adenosine A1 Receptor Antagonists; D000818:Animals; D000831:Animals, Newborn; D001640:Bicuculline / Q000494:pharmacology; D003517:Cyclopentanes / Q000494:pharmacology; D003521:Cyclopropanes / Q000494:pharmacology; D004307:Dose-Response Relationship, Radiation; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D018756:GABA Antagonists / Q000494:pharmacology; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019599:Mossy Fibers, Hippocampal / Q000187:drug effects / Q000502:physiology*; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D009474:Neurons / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D018408:Patch-Clamp Techniques / Q000379:methods; D051381:Rats; D017208:Rats, Wistar; D043682:Receptor, Adenosine A1 / Q000172:deficiency; D013569:Synapses / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D009435:Synaptic Transmission / Q000502:physiology*; D014970:Xanthines / Q000494:pharmacology
chemical_list: D058916:Adenosine A1 Receptor Antagonists; D003517:Cyclopentanes; D003521:Cyclopropanes; D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D043682:Receptor, Adenosine A1; D014970:Xanthines; C494075:cyclopentenyladenine; C082313:2-(2,3-dicarboxycyclopropyl)glycine; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; C051360:1,3-dipropyl-8-cyclopentylxanthine; D000225:Adenine; D000241:Adenosine; D005998:Glycine; D001640:Bicuculline