Astrocytes Are Endogenous Regulators of Basal Transmission at Central Synapses

SummaryBasal synaptic transmission involves the release of neurotransmitters at individual synapses in response to a single action potential. Recent discoveries show that astrocytes modulate the activity of neuronal networks upon sustained and intense synaptic activity. However, their ability to regulate basal synaptic transmission remains ill defined and controversial. Here, we show that astrocytes in the hippocampal CA1 region detect synaptic activity induced by single-synaptic stimulation. Astrocyte activation occurs at functional compartments found along astrocytic processes and involves metabotropic glutamate subtype 5 receptors. In response, astrocytes increase basal synaptic transmission, as revealed by the blockade of their activity with a Ca2+ chelator. Astrocytic modulation of basal synaptic transmission is mediated by the release of purines and the activation of presynaptic A2A receptors by adenosine. Our work uncovers an essential role for astrocytes in the regulation of elementary synaptic communication and provides insight into fundamental aspects of brain function.

Graphical AbstractFigure optionsDownload high-quality image (350 K)Download as PowerPoint slideHighlights
► Astrocytic processes are organized in discrete functional compartments
► A single synaptic stimulation evokes Ca2+ signals in astrocytes via mGluR5 receptor
► Ca2+ signals activate astrocytes, eliciting purine release
► Astrocytes upregulate basal synaptic transmission through presynaptic A2A receptors