Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


Logo for

Science 339 (6116): 197-200

Copyright © 2013 by the American Association for the Advancement of Science

Glutamate-Dependent Neuroglial Calcium Signaling Differs Between Young and Adult Brain

Wei Sun,1,* Evan McConnell,1,* Jean-Francois Pare,2,* Qiwu Xu,1,* Michael Chen,1 Weiguo Peng,1 Ditte Lovatt,1 Xiaoning Han,1 Yoland Smith,2 Maiken Nedergaard1,{dagger}

Abstract: An extensive literature shows that astrocytes exhibit metabotropic glutamate receptor 5 (mGluR5)–dependent increases in cytosolic calcium ions (Ca2+) in response to glutamatergic transmission and, in turn, modulate neuronal activity by their Ca2+-dependent release of gliotransmitters. These findings, based on studies of young rodents, have led to the concept of the tripartite synapse, in which astrocytes actively participate in neurotransmission. Using genomic analysis, immunoelectron microscopy, and two-photon microscopy of astrocytic Ca2+ signaling in vivo, we found that astrocytic expression of mGluR5 is developmentally regulated and is undetectable after postnatal week 3. In contrast, mGluR3, whose activation inhibits adenylate cyclase but not calcium signaling, was expressed in astrocytes at all developmental stages. Neuroglial signaling in the adult brain may therefore occur in a manner fundamentally distinct from that exhibited during development.

1 Division of Glial Disease and Therapeutics, Center for Translational Neuromedicine, University of Rochester, Rochester, NY 14642, USA.
2 Yerkes National Primate Research Center and Department of Neurology, Emory University, 954 Gatewood Road NE, Atlanta, GA 30329, USA.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: Nedergaard{at}

Neurovascular signaling in the brain and the pathological consequences of hypertension.
K. M. Dunn and M. T. Nelson (2014)
Am J Physiol Heart Circ Physiol 306, H1-H14
   Abstract »    Full Text »    PDF »
Rapid stimulus-evoked astrocyte Ca2+ elevations and hemodynamic responses in mouse somatosensory cortex in vivo.
B. L. Lind, A. R. Brazhe, S. B. Jessen, F. C. C. Tan, and M. J. Lauritzen (2013)
PNAS 110, E4678-E4687
   Abstract »    Full Text »    PDF »
Photolysis of Caged Ca2+ But Not Receptor-Mediated Ca2+ Signaling Triggers Astrocytic Glutamate Release.
F. Wang, N. A. Smith, Q. Xu, S. Goldman, W. Peng, J. H. Huang, T. Takano, and M. Nedergaard (2013)
J. Neurosci. 33, 17404-17412
   Abstract »    Full Text »    PDF »
Astrocyte regulation of cerebral vascular tone.
J. A. Filosa and J. A. Iddings (2013)
Am J Physiol Heart Circ Physiol 305, H609-H619
   Abstract »    Full Text »    PDF »
In vivo Stimulus-Induced Vasodilation Occurs without IP3 Receptor Activation and May Precede Astrocytic Calcium Increase.
K. Nizar, H. Uhlirova, P. Tian, P. A. Saisan, Q. Cheng, L. Reznichenko, K. L. Weldy, T. C. Steed, V. B. Sridhar, C. L. MacDonald, et al. (2013)
J. Neurosci. 33, 8411-8422
   Abstract »    Full Text »    PDF »
Imaging calcium microdomains within entire astrocyte territories and endfeet with GCaMPs expressed using adeno-associated viruses.
E. Shigetomi, E. A. Bushong, M. D. Haustein, X. Tong, O. Jackson-Weaver, S. Kracun, J. Xu, M. V. Sofroniew, M. H. Ellisman, and B. S. Khakh (2013)
J. Gen. Physiol. 141, 633-647
   Abstract »    Full Text »    PDF »
Of changing glial responses, modular interactions, and why a worm may turn.
E. M. Adler (2013)
J. Gen. Physiol. 141, 273-274
   Full Text »    PDF »
Developmental Refining of Neuroglial Signaling?.
A. Grosche and A. Reichenbach (2013)
Science 339, 152-153
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882