Radially expanding transglial calcium waves in the intact cerebellum

doi:10.1073/pnas.0809269106

Radially expanding transglial calcium waves in the intact cerebellum

^aDepartment of Molecular Biology and
^bPrinceton Neuroscience Institute, Princeton University, Lewis Thomas Laboratory, Washington Road, Princeton, NJ 08544;
^cBrain Research Institute, University of Zürich, Winterthurerstrasse 190, 8057 Zürich, Switzerland; and
^dLaboratory for Memory and Learning, RIKEN Brain Science Institute, 2-1, Hirosawa, Wako-shi, Saitama 351-0198, Japan

Edited by Charles F. Stevens, The Salk Institute for Biological Studies, La Jolla, CA, and approved January 14, 2009
↵¹T.M.H. and B.K. contributed equally to this work. (received for review September 16, 2008)

Abstract

Multicellular glial calcium waves may locally regulate neural activity or brain energetics. Here, we report a diffusion-driven astrocytic signal in the normal, intact brain that spans many astrocytic processes in a confined volume without fully encompassing any one cell. By using 2-photon microscopy in rodent cerebellar cortex labeled with fluorescent indicator dyes or the calcium-sensor protein G-CaMP2, we discovered spontaneous calcium waves that filled approximately ellipsoidal domains of Bergmann glia processes. Waves spread in 3 dimensions at a speed of 4–11 μm/s to a diameter of ≈50 μm, slowed during expansion, and were reversibly blocked by P2 receptor antagonists. Consistent with the hypothesis that ATP acts as a diffusible trigger of calcium release waves, local ejection of ATP triggered P2 receptor-mediated waves that were refractory to repeated activation. Transglial waves represent a means for purinergic signals to act with local specificity to modulate activity or energetics in local neural circuits.

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Footnotes

²To whom correspondence may be addressed. E-mail: hoogland{at}princeton.edu, bkuhn{at}princeton.edu, or sswang{at}princeton.edu
Author contributions: T.M.H., B.K., W.G., F.H., and S.S.-H.W. designed research; T.M.H., B.K., and W.G. performed research; T.M.H., B.K., W.G., W.H., J.N., F.H., and J.F. contributed new reagents/analytic tools; T.M.H. and B.K. analyzed data; and T.M.H., B.K., F.H., and S.S.-H.W. wrote the paper.
↵³Present address: Saitama University Brain Science Institute, 255 Shimo-Okubo, Sakura-ku, Saitama City, Saitama 338-8570, Japan.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
This article contains supporting information online at www.pnas.org/cgi/content/full/0809269106/DCSupplemental.
↵† Nimmerjahn A, Mukamel EA, Schnitzer MJ, Neuroscience 2008, November 15–19, 2008, Washington, DC, abstr 337.2.