Local Ca2+ detection and modulation of synaptic release by astrocytes

Nat Neurosci. 2011 Sep 11;14(10):1276-84. doi: 10.1038/nn.2929.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / drug effects
  • Action Potentials / physiology
  • Adenosine Diphosphate / analogs & derivatives
  • Adenosine Diphosphate / pharmacology
  • Animals
  • Animals, Newborn
  • Astrocytes / drug effects
  • Astrocytes / physiology*
  • Astrocytes / ultrastructure
  • Biophysics
  • Calcium / metabolism*
  • Calcium Signaling / drug effects
  • Calcium Signaling / physiology*
  • Cell Communication / drug effects
  • Cell Communication / physiology
  • Chelating Agents / pharmacology
  • Egtazic Acid / analogs & derivatives
  • Egtazic Acid / pharmacology
  • Electric Stimulation / methods
  • Enzyme Inhibitors / pharmacology
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / genetics
  • Heparin / pharmacology
  • Hippocampus / cytology
  • In Vitro Techniques
  • Inositol 1,4,5-Trisphosphate Receptors / deficiency
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Models, Biological
  • Patch-Clamp Techniques
  • Purinergic P2Y Receptor Antagonists / pharmacology
  • Sodium Channel Blockers / pharmacology
  • Sucrose / pharmacology
  • Synapses / drug effects
  • Synapses / metabolism*
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology
  • Tetrodotoxin / pharmacology
  • Thapsigargin / pharmacology

Substances

  • Chelating Agents
  • Enzyme Inhibitors
  • Inositol 1,4,5-Trisphosphate Receptors
  • N(6)-methyl-2'-deoxyadenosine 3',5'-diphosphate
  • Purinergic P2Y Receptor Antagonists
  • Sodium Channel Blockers
  • Tetrodotoxin
  • Egtazic Acid
  • Sucrose
  • Adenosine Diphosphate
  • Thapsigargin
  • Heparin
  • 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid
  • Calcium