Neurons are central to the transfer of information in the brain through the release of neurotransmitters at synapses. Astrocytes, a type of glial cell, were thought merely to support neurons; however, they are now understood to also modulate synaptic transmission during intense synaptic activity through their ability to detect neurotransmitters, such as glutamate, and release gliotransmitters, such as purines (see the Commentary by Navarrete and Araque). Panatier et al. investigated whether this neuromodulatory role of astrocytes extended to the regulation of basal synaptic transmission at individual synapses in response to a single action potential. Fast confocal Ca2+ imaging in rat hippocampal slices revealed the occurrence of spontaneous, localized Ca2+ signaling in distinct compartments along astrocytic processes. Stimulation of pyramidal neuronal presynaptic elements with single electrical pulses resulted in similar Ca2+ responses in astrocytes that were spatially localized and occurred simultaneously with excitatory postsynaptic currents (EPSCs). Treatment of astrocytes with the Ca2+ chelator BAPTA increased the failure rate of EPSCs, indicating decreased synaptic efficacy. Blockade of the metabotropic glutamate receptor mGluR5 with the antagonist MPEP reduced the Ca2+ responses in astrocytes in response to synaptic stimulation and resulted in an increased EPSC failure rate. Pretreatment of the astrocytes with BAPTA blocked the ability of MPEP to reduce synaptic efficacy, suggesting that Ca2+ signaling was required for the mGluR5-dependent effect on transmission. Experiments with the adenosine A2A receptor antagonist SCH 58261 suggested that mGluR5-dependent enhancement of basal synaptic transmission depended on astrocyte-derived adenosine. Finally, immunohistochemical analysis of hippocampal slices showed the compartmentalized localization of mGluR5 along astrocytic processes in apposition to A2A receptor–positive presynaptic elements. Together, these data suggest that in addition to detecting synaptic activity by single action potentials through mGluR5, astrocytes release adenosine in a feedback mechanism that enhances basal synaptic transmission.
A. Panatier, J. Vallée, M. Haber, K. K. Murai, J.-C. Lacaille, R. Robitaille, Astrocytes are endogenous regulators of basal transmission at central synapses. Cell 146, 785–798 (2011). [PubMed]
M. Navarrete, A. Araque, Basal synaptic transmission: Astrocytes rule! Cell 146, 675–677 (2011). [PubMed]