Selective stimulation of astrocyte calcium in situ does not affect neuronal excitatory synaptic activity.
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.
Fiacco
Todd A
TA
Department of Pharmacology, 1004 Mary Ellen Jones Building CB# 7365, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7365, USA.
Agulhon
Cendra
C
Taves
Sarah R
SR
Petravicz
Jeremy
J
Casper
Kristen B
KB
Dong
Xinzhong
X
Chen
Ju
J
McCarthy
Ken D
KD
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*
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