title: Intracellular astrocyte calcium waves in situ increase the frequency of spontaneous AMPA receptor currents in CA1 pyramidal neurons.
abstract: Spontaneous neurotransmitter release and activation of group I metabotropic glutamate receptors (mGluRs) each play a role in the plasticity of neuronal synapses. Astrocytes may contribute to short- and long-term synaptic changes by signaling to neurons via these processes. Spontaneous whole-cell AMPA receptor (AMPAR) currents were recorded in CA1 pyramidal cells in situ while evoking Ca2+ increases in the adjacent stratum radiatum astrocytes by uncaging IP3. Whole-cell patch clamp was used to deliver caged IP3 and the Ca2+ indicator dye Oregon green BAPTA-1 to astrocytes. Neurons were patch-clamped and filled with Alexa 568 hydrazide dye to visualize their morphological relationship to the astrocyte. On uncaging of IP3, astrocyte Ca2+ responses reliably propagated as a wave into the very fine distal processes, synchronizing Ca2+ activity within astrocyte microdomains. The intracellular astrocyte Ca2+ wave coincided with a significant increase in the frequency of AMPA spontaneous EPSCs, but with no change in their kinetics. AMPAR current amplitudes were increased as well, but not significantly (p = 0.06). The increased frequency of AMPAR currents was sensitive to the group I mGluR antagonists LY367385 and 2-methyl-6-(phenylethynyl)-pyridine, suggesting that (1) astrocytes released glutamate in response to IP3 uncaging, and (2) glutamate released by astrocytes activated group I mGluRs to facilitate the release of glutamate from excitatory neuronal presynaptic boutons. These results extend previous studies, which have shown astrocyte modulation of neuronal activity in vitro and suggest that astrocyte-to-neuron signaling in intact tissue may contribute to synaptic plasticity.
authors.affiliation: Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7365, USA.
authors.forename: Todd A
authors.initials: TA
authors.lastname: Fiacco
authors.forename: Ken D
authors.initials: KD
authors.lastname: McCarthy
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D002450:Cell Communication / Q000187:drug effects / Q000502:physiology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D005456:Fluorescent Dyes; D018698:Glutamic Acid / Q000378:metabolism; D049452:Green Fluorescent Proteins; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D066298:In Vitro Techniques; D015544:Inositol 1,4,5-Trisphosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D042541:Intracellular Space / Q000378:metabolism*; D007478:Iontophoresis; D008164:Luminescent Proteins / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018408:Patch-Clamp Techniques; D017966:Pyramidal Cells / Q000378:metabolism*; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D018691:Excitatory Amino Acid Antagonists; D005456:Fluorescent Dyes; D008164:Luminescent Proteins; D018091:Receptors, AMPA; C061868:inositol 1,4,5-trisphosphate 1-(2-nitrophenyl)ethyl ester; D049452:Green Fluorescent Proteins; D018698:Glutamic Acid; D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium