title: Selective stimulation of astrocyte calcium in situ does not affect neuronal excitatory synaptic activity.
abstract: Astrocytes are considered the third component of the synapse, responding to neurotransmitter release from synaptic terminals and releasing gliotransmitters--including glutamate--in a Ca(2+)-dependent manner to affect neuronal synaptic activity. Many studies reporting astrocyte-driven neuronal activity have evoked astrocyte Ca(2+) increases by application of endogenous ligands that directly activate neuronal receptors, making astrocyte contribution to neuronal effect(s) difficult to determine. We have made transgenic mice that express a Gq-coupled receptor only in astrocytes to evoke astrocyte Ca(2+) increases using an agonist that does not bind endogenous receptors in brain. By recording from CA1 pyramidal cells in acute hippocampal slices from these mice, we demonstrate that widespread Ca(2+) elevations in 80%-90% of stratum radiatum astrocytes do not increase neuronal Ca(2+), produce neuronal slow inward currents, or affect excitatory synaptic activity. Our findings call into question the developing consensus that Ca(2+)-dependent glutamate release by astrocytes directly affects neuronal synaptic activity in situ.
authors.affiliation: Department of Pharmacology, 1004 Mary Ellen Jones Building CB# 7365, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7365, USA.
authors.forename: Todd A
authors.initials: TA
authors.lastname: Fiacco
authors.forename: Cendra
authors.initials: C
authors.lastname: Agulhon
authors.forename: Sarah R
authors.initials: SR
authors.lastname: Taves
authors.forename: Jeremy
authors.initials: J
authors.lastname: Petravicz
authors.forename: Kristen B
authors.initials: KB
authors.lastname: Casper
authors.forename: Xinzhong
authors.initials: X
authors.lastname: Dong
authors.forename: Ju
authors.initials: J
authors.lastname: Chen
authors.forename: Ken D
authors.initials: KD
authors.lastname: McCarthy
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D002450:Cell Communication / Q000502:physiology; D004347:Drug Interactions; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000235:genetics; D006624:Hippocampus / Q000166:cytology; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018377:Neurotransmitter Agents / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology; D018408:Patch-Clamp Techniques / Q000379:methods; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D017729:Presynaptic Terminals / Q000187:drug effects / Q000502:physiology; D017966:Pyramidal Cells / Q000166:cytology / Q000502:physiology*; D043562:Receptors, G-Protein-Coupled / Q000235:genetics; D013569:Synapses / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
chemical_list: C470191:MrgA1 protein, mouse; D018377:Neurotransmitter Agents; D009842:Oligopeptides; D043562:Receptors, G-Protein-Coupled; D049452:Green Fluorescent Proteins; C066148:phenylalanyl-leucyl-arginyl phenylalaninamide; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D010751:Phosphopyruvate Hydratase; D002118:Calcium