title: Local Ca2+ detection and modulation of synaptic release by astrocytes.
abstract: Astrocytes communicate with synapses by means of intracellular calcium ([Ca(2+)](i)) elevations, but local calcium dynamics in astrocytic processes have never been thoroughly investigated. By taking advantage of high-resolution two-photon microscopy, we identify the characteristics of local astrocyte calcium activity in the adult mouse hippocampus. Astrocytic processes showed intense activity, triggered by physiological transmission at neighboring synapses. They encoded synchronous synaptic events generated by sparse action potentials into robust regional (∼12 μm) [Ca(2+)](i) elevations. Unexpectedly, they also sensed spontaneous synaptic events, producing highly confined (∼4 μm), fast (millisecond-scale) miniature Ca(2+) responses. This Ca(2+) activity in astrocytic processes is generated through GTP- and inositol-1,4,5-trisphosphate-dependent signaling and is relevant for basal synaptic function. Thus, buffering astrocyte [Ca(2+)](i) or blocking a receptor mediating local astrocyte Ca(2+) signals decreased synaptic transmission reliability in minimal stimulation experiments. These data provide direct evidence that astrocytes are integrated in local synaptic functioning in adult brain.
authors: Department of Cell Biology and Morphology, University of Lausanne, Lausanne, Switzerland.
authors: Maria Amalia
authors: MA
authors: Di Castro
authors: Julien
authors: J
authors: Chuquet
authors: Nicolas
authors: N
authors: Liaudet
authors: Khaleel
authors: K
authors: Bhaukaurally
authors: Mirko
authors: M
authors: Santello
authors: David
authors: D
authors: Bouvier
authors: Pascale
authors: P
authors: Tiret
authors: Andrea
authors: A
authors: Volterra
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000244:Adenosine Diphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D001703:Biophysics; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D002450:Cell Communication / Q000187:drug effects / Q000502:physiology; D002614:Chelating Agents / Q000494:pharmacology; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004558:Electric Stimulation / Q000379:methods; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D006493:Heparin / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology; D066298:In Vitro Techniques; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000172:deficiency; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008954:Models, Biological; D018408:Patch-Clamp Techniques; D058921:Purinergic P2Y Receptor Antagonists / Q000494:pharmacology; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013395:Sucrose / Q000494:pharmacology; D013569:Synapses / Q000187:drug effects / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D013779:Tetrodotoxin / Q000494:pharmacology; D019284:Thapsigargin / Q000494:pharmacology
chemical_list: D002614:Chelating Agents; D004791:Enzyme Inhibitors; D053496:Inositol 1,4,5-Trisphosphate Receptors; C111914:N(6)-methyl-2'-deoxyadenosine 3',5'-diphosphate; D058921:Purinergic P2Y Receptor Antagonists; D026941:Sodium Channel Blockers; D013779:Tetrodotoxin; D004533:Egtazic Acid; D013395:Sucrose; D000244:Adenosine Diphosphate; D019284:Thapsigargin; D006493:Heparin; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D002118:Calcium