Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Upstream current for a downstream flow

Nature Neuroscience volume 20, pages 631–633 (2017)Cite this article

Subjects

Capillary endothelial cells sense neuronal activity-evoked increases in extracellular K+ via KIR2.1 inwardly rectifying K+ channels. The ensuing hyperpolarization travels upstream along the vascular network, reaching arterioles and evoking vasodilation.

The streams of blood that feed the brain flow through ever-narrowing courses, from pial arteries on the brain's surface to penetrating parenchymal arterioles and, ultimately, to capillaries, the smallest of all vessels. But the actual distribution of blood throughout the brain is not fixed. Instead, it varies according to regional moment-to-moment needs for nutrients as a result of neuronal activity. This on-demand process of redirecting blood to areas of greater need, termed neurovascular coupling (NVC)—the physiological basis of functional MRI techniques—is necessary because neurons have a very limited capacity to store energetic substrates. To obtain the nutrients they need, neurons must somehow communicate their energy status to upstream elements of the cerebrovasculature. Yet while much has been learned—and debated—about the mechanisms that evoke changes in cerebral blood flow in response to increases in neuronal activity, many fundamental questions remain, including what parts of the vascular tree neurons signal to, how this signal is detected and, most importantly, how the signal is transmitted upstream to arterioles and pial arteries to dilate these vessels along the path that leads to areas where neurons are active. Increasingly, pericytes, which reside on capillaries, and the red blood cells coursing through the capillaries are being viewed as receiving signals from neurons and astrocytes1,2,3,4. These perspectives reflect, in part, a growing appreciation of the vast coverage of the capillary network—which encompasses some 400 miles (nearly 650 km) in the human brain5—and the close apposition of capillary segments to hungry, working neurons.

This is a preview of subscription content, access via your institution

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

Buy

All prices are NET prices.

Figure 1: Upstream endothelial cell conduction of a hyperpolarizing current following increases in neuronal activity.

References

  1. Wei, H.S. et al. Neuron 91, 851–862 (2016).

    Article  CAS  Google Scholar 

  2. Hall, C.N. et al. Nature 508, 55–60 (2014).

    Article  CAS  Google Scholar 

  3. Kornfield, T.E. & Newman, E.A. J. Neurosci. 34, 11504–11513 (2014).

    Article  Google Scholar 

  4. Mishra, A. et al. Nat. Neurosci. 19, 1619–1627 (2016).

    Article  CAS  Google Scholar 

  5. Zlokovic, B.V. Trends Neurosci. 28, 202–208 (2005).

    Article  CAS  Google Scholar 

  6. Longden, T.A. et al. Nat. Neurosci. 20, 717–726 (2017).

    Article  CAS  Google Scholar 

  7. Hannah, R.M., Dunn, K.M., Bonev, A.D. & Nelson, M.T. J. Cereb. Blood Flow Metab. 31, 1175–1186 (2011).

    Article  CAS  Google Scholar 

  8. Ayata, C. & Lauritzen, M. Physiol. Rev. 95, 953–993 (2015).

    Article  CAS  Google Scholar 

  9. Kofuji, P. & Newman, E.A. Neuroscience 129, 1043–1054 (2004).

    Article  Google Scholar 

  10. Olsen, M.L. & Sontheimer, H. J. Neurochem. 107, 589–601 (2008).

    Article  CAS  Google Scholar 

  11. Attwell, D. et al. Nature 468, 232–243 (2010).

    Article  CAS  Google Scholar 

  12. Lecrux, C. & Hamel, E. Acta Physiol. (Oxf.) 203, 47–59 (2011).

    Article  CAS  Google Scholar 

  13. Simard, M., Arcuino, G., Takano, T., Liu, Q.S. & Nedergaard, M. J. Neurosci. 23, 9254–9262 (2003).

    Article  CAS  Google Scholar 

  14. Girouard, H. et al. Proc. Natl. Acad. Sci. USA 107, 3811–3816 (2010).

    Article  CAS  Google Scholar 

  15. Filosa, J.A. et al. Nat. Neurosci. 9, 1397–1403 (2006).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Jessica A. Filosa is in the Department of Physiology, Augusta University, Augusta, Georgia, USA.,

    Jessica A Filosa

Authors
  1. Jessica A Filosa
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jessica A Filosa.

Ethics declarations

Competing interests

The author declares no competing financial interests.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Filosa, J. Upstream current for a downstream flow. Nat Neurosci 20, 631–633 (2017). https://doi.org/10.1038/nn.4542

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nn.4542

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing