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Sci. Signal., 24 January 2012
Vol. 5, Issue 208, p. ra8
[DOI: 10.1126/scisignal.2002160]


Extracellular Ca2+ Acts as a Mediator of Communication from Neurons to Glia

Arnulfo Torres1, Fushun Wang1, Qiwu Xu1, Takumi Fujita1, Radoslaw Dobrowolski2, Klaus Willecke2, Takahiro Takano1, and Maiken Nedergaard1*

1 Center for Translational Neuromedicine, Division of Glial Disease and Therapeutics, University of Rochester Medical School, 601 Elmwood Avenue, Rochester, NY 14642, USA.
2 Institut fuer Genetik, Rheinische Friedrich-Wilhelms-Universitaet, D-53115 Bonn, Germany.

Abstract: Defining the pathways through which neurons and astrocytes communicate may contribute to the elucidation of higher central nervous system functions. We investigated the possibility that decreases in extracellular calcium ion concentration ([Ca2+]e) that occur during synaptic transmission might mediate signaling from neurons to glia. Using noninvasive photolysis of the photolabile Ca2+ buffer diazo-2 {N-[2-[2-[2-[bis(carboxymethyl)amino]-5-(diazoacetyl)phenoxy]ethoxy]-4-methylphenyl]-N-(carboxymethyl)-, tetrapotassium salt} to reduce [Ca2+]e or caged glutamate to simulate glutamatergic transmission, we found that a local decline in extracellular Ca2+ triggered astrocytic adenosine triphosphate (ATP) release and astrocytic Ca2+ signaling. In turn, activation of purinergic P2Y1 receptors on a subset of inhibitory interneurons initiated the generation of action potentials by these interneurons, thereby enhancing synaptic inhibition. Thus, astrocytic ATP release evoked by an activity-associated decrease in [Ca2+]e may provide a negative feedback mechanism that potentiates inhibitory transmission in response to local hyperexcitability.

* To whom correspondence should be addressed. E-mail: nedergaard{at}

Citation: A. Torres, F. Wang, Q. Xu, T. Fujita, R. Dobrowolski, K. Willecke, T. Takano, M. Nedergaard, Extracellular Ca2+ Acts as a Mediator of Communication from Neurons to Glia. Sci. Signal. 5, ra8 (2012).

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