Cell calcium signaling mediates capillary regulation of blood flow in the Retina

Kyle R. Biesecker, Anja I. Srienc, Angela M. Shimoda, Amit Agarwal, Dwight E. Bergles, Paulo Kofuji, Eric A. Newman

Research output: Contribution to journalArticlepeer-review

83 Scopus citations


The brain is critically dependent on the regulation of blood flow to nourish active neurons. One widely held hypothesis of blood flow regulation holds that active neurons stimulate Ca2+ increases in glial cells, triggering glial release of vasodilating agents. This hypothesis has been challenged, as arteriole dilation can occur in the absence of glial Ca2+ signaling. We address this controversy by imaging glial Ca2+ signaling and vessel dilation in the mouse retina. We find that sensory stimulation results in Ca2+ increases in the glial endfeet contacting capillaries, but not arterioles, and that capillary dilations often follow spontaneous Ca2+ signaling. In IP3R2−/− mice, where glial Ca2+ signaling is reduced, light-evoked capillary, but not arteriole, dilation is abolished. The results show that, independent of arterioles, capillaries actively dilate and regulate blood flow. Furthermore, the results demonstrate that glial Ca2+ signaling regulates capillary but not arteriole blood flow.

Original languageEnglish (US)
Pages (from-to)9435-9445
Number of pages11
JournalJournal of Neuroscience
Issue number36
StatePublished - Sep 7 2016

Bibliographical note

Funding Information:
This work was supported by NIH Grants R01-EY04077 and P30-EY11374 (E.A.N.) and P50-MH084020 and P30- NS050274 (D.E.B.), MinnCReST Predoctoral Training Fellowship T90 DE 022732, and the NIH Predoctoral Training of Neuroscientists Grant T32GMOD8471. We thank David Attwell, Anusha Mishra, Alfonso Araque, and Joanna Kur for helpful discussions, and Heidi Ro¨ehrich for immunohistochemistry assistance.

Publisher Copyright:
© 2016 the authors.


  • Blood flow
  • Calcium signaling
  • Capillary
  • Glia
  • Neurovascular coupling
  • Retina


Dive into the research topics of 'Cell calcium signaling mediates capillary regulation of blood flow in the Retina'. Together they form a unique fingerprint.

Cite this