title: Hippocampal astrocytes in situ exhibit calcium oscillations that occur independent of neuronal activity.
abstract: Results presented in this study indicate that a large subpopulation (approximately 65%) of hippocampal astrocytes in situ exhibit calcium oscillations in the absence of neuronal activity. Further, the spontaneous oscillations observed within individual hippocampal astrocytes generally developed asynchronously throughout the astrocyte's fine processes and occasionally spread through a portion of that astrocyte as a calcium wave but do not appear to spread among astrocytes as an intercellular calcium wave. Bath application of cyclopiazonic acid and injection of individual astrocytes with heparin blocked astrocytic calcium oscillations. Application of tetrodotoxin or incubation of slices with bafilomycin A1 had no effect on astrocytic calcium oscillations but did block evoked and spontaneous postsynaptic currents measured in CA1 pyramidal neurons. Application of a cocktail of antagonists for metabotropic glutamate receptors and purinergic receptors had no effect on the astrocytic calcium oscillations but blocked the ability of purinergic and metabotropic glutamatergic agonists to increase astrocytic calcium levels. These results indicate that the spontaneous calcium oscillations observed in hippocampal astrocytes in situ are mediated by IP3 receptor activation, are not dependent on neuronal activity, and do not depend on activation of metabotropic glutamate receptors or purinergic receptors. To our knowledge, this is the first demonstration that astrocytes in situ exhibit intrinsic signaling. This finding supports the hypothesis that astrocytes, independent of neuronal input, may act as pacemakers to modulate neuronal activity in situ.
authors.affiliation: Department of Pharmacology, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599-7365, USA.
authors.forename: Wolfgang J
authors.initials: WJ
authors.lastname: Nett
authors.forename: Scott H
authors.initials: SH
authors.lastname: Oloff
authors.forename: Ken D
authors.initials: KD
authors.lastname: McCarthy
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D001683:Biological Clocks / Q000187:drug effects / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000502:physiology*; D002135:Calcium-Binding Proteins; D022081:Cell Surface Extensions / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005456:Fluorescent Dyes; D006493:Heparin / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D007424:Intracellular Fluid / Q000378:metabolism; D018942:Macrolides; D051379:Mice; D008840:Microfilament Proteins; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D058913:Purinergic Agonists; D058914:Purinergic Antagonists; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000037:antagonists & inhibitors; D013779:Tetrodotoxin / Q000494:pharmacology
chemical_list: C112986:AIF1 protein, human; D000900:Anti-Bacterial Agents; D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D005456:Fluorescent Dyes; D007211:Indoles; D018942:Macrolides; D008840:Microfilament Proteins; D058913:Purinergic Agonists; D058914:Purinergic Antagonists; D018094:Receptors, Metabotropic Glutamate; D013779:Tetrodotoxin; C040929:bafilomycin A1; D006493:Heparin; D002118:Calcium; C000543:cyclopiazonic acid