title: Adenosine as an endogenous regulating factor of hippocampal sharp waves.
abstract: The rodent hippocampus exhibits population activities called sharp waves (SPWs) during slow wave sleep and wake immobility. SPWs are important for hippocampal-cortical communication and memory consolidation, and abnormal sharp wave-ripple complexes are closely related to epileptic seizures. Although the SPWs are known to arise from the CA3 circuit, the local mechanisms underlying their generation are not fully understood. We hypothesize that endogenous adenosine is a local regulator of hippocampal SPWs. We tested this hypothesis in thick mouse hippocampal slices that encompass a relatively large hippocampal circuit and have a high propensity of generating spontaneous in vitro SPWs. We found that application of adenosine A1 receptor antagonists induced in vitro SPWs and that such induction was sensitive to blockade by NMDA receptor antagonists. By contrast, an increase in endogenous adenosine via pharmacological inhibition of adenosine transporters or adenosine degrading enzymes suppressed spontaneous in vitro SPWs. We thus suggest that the initiation and incidence of sharp wave-like population events are under tight control by the activity of endogenously stimulated A1 receptors.
authors.affiliation: Toronto Western Research Institute, Division of Fundamental Neurobiology, University Health Network, Toronto, Ontario, Canada.
authors.forename: Chiping
authors.initials: C
authors.lastname: Wu
authors.forename: Teser
authors.initials: T
authors.lastname: Wong
authors.forename: Xiadi
authors.initials: X
authors.lastname: Wu
authors.forename: Evan
authors.initials: E
authors.lastname: Sheppy
authors.forename: Liang
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000241:Adenosine / Q000378:metabolism*; D058916:Adenosine A1 Receptor Antagonists; D000818:Animals; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008839:Microelectrodes; D033703:Nucleoside Transport Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D018408:Patch-Clamp Techniques; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism; D011810:Quinoxalines / Q000494:pharmacology; D043682:Receptor, Adenosine A1 / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology; D014970:Xanthines / Q000494:pharmacology
chemical_list: D058916:Adenosine A1 Receptor Antagonists; D033703:Nucleoside Transport Proteins; D011810:Quinoxalines; D043682:Receptor, Adenosine A1; D016194:Receptors, N-Methyl-D-Aspartate; D014970:Xanthines; C444719:adenosine transporter; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; C010192:9-(2-hydroxy-3-nonyl)adenine; D016291:Dizocilpine Maleate; C031433:8-(4-sulfophenyl)theophylline; C051360:1,3-dipropyl-8-cyclopentylxanthine; D013806:Theophylline; D000225:Adenine; D000241:Adenosine