title: An in vitro model of hippocampal sharp waves: regional initiation and intracellular correlates.
abstract: During slow wave sleep and consummatory behaviors, electroencephalographic recordings from the rodent hippocampus reveal large amplitude potentials called sharp waves. The sharp waves originate from the CA3 circuitry and their generation is correlated with coherent discharges of CA3 pyramidal neurons and dependent on activities mediated by AMPA glutamate receptors. To model sharp waves in a relatively large hippocampal circuitry in vitro, we developed thick (1 mm) mouse hippocampal slices by separating the dentate gyrus from the CA2/CA1 areas while keeping the functional dentate gyrus-CA3-CA1 connections. We found that large amplitude (0.3-3 mV) sharp wave-like field potentials occurred spontaneously in the thick slices without extra ionic or pharmacological manipulation and they resemble closely electroencephalographic sharp waves with respect to waveform, regional initiation, pharmacological manipulations, and intracellular correlates. Through measuring tissue O2, K+, and synaptic and single cell activities, we verified that the sharp wave-like potentials are not a consequence of anoxia, nonspecific elevation of extracellular K+ and dissection-related tissue damage. Our data suggest that a subtle but crucial increase in the CA3 glutamatergic activity effectively recruits a population of neurons thus responsible for the generation of the sharp wave-like spontaneous field potentials in isolated hippocampal circuitry.
authors.affiliation: Toronto Western Research Institute, University Health Network, Department of Medicine, University of Toronto, Ontario, Canada.
authors.forename: Chiping
authors.initials: C
authors.lastname: Wu
authors.forename: Marjan Nassiri
authors.initials: MN
authors.lastname: Asl
authors.forename: Jesse
authors.initials: J
authors.lastname: Gillis
authors.forename: Frances K
authors.initials: FK
authors.lastname: Skinner
authors.forename: Liang
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000704:Analysis of Variance; D000777:Anesthetics / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001640:Bicuculline / Q000494:pharmacology; D002614:Chelating Agents / Q000494:pharmacology; D004307:Dose-Response Relationship, Radiation; D004347:Drug Interactions; D004533:Egtazic Acid / Q000494:pharmacology; D004558:Electric Stimulation / Q000379:methods; D004566:Electrodes; D005071:Evoked Potentials / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D005110:Extracellular Space / Q000378:metabolism*; D018756:GABA Antagonists / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology* / Q000502:physiology; D000860:Hypoxia / Q000503:physiopathology; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D008723:Methohexital / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D009434:Neural Pathways / Q000502:physiology; D009474:Neurons / Q000145:classification / Q000187:drug effects / Q000502:physiology*; D010100:Oxygen / Q000378:metabolism; D018408:Patch-Clamp Techniques / Q000379:methods; D011188:Potassium / Q000378:metabolism; D009435:Synaptic Transmission
chemical_list: D000777:Anesthetics; D002614:Chelating Agents; D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D004533:Egtazic Acid; D008723:Methohexital; D011188:Potassium; D010100:Oxygen; D001640:Bicuculline