Cell type specificity of neurovascular coupling in cerebral cortex

  1. Hana Uhlirova
  2. Kıvılcım Kılıç
  3. Peifang Tian
  4. Martin Thunemann
  5. Michele Desjardins
  6. Payam A Saisan
  7. Sava Sakadžić
  8. Torbjørn V Ness
  9. Celine Mateo
  10. Qun Cheng
  11. Kimberly L Weldy
  12. Florence Razoux
  13. Matthieu Vanderberghe
  14. Jonathan A Cremonesi
  15. Christopher GL Ferri
  16. Krystal Nizar
  17. Vishnu B Sridhar
  18. Tyler C Steed
  19. Maxim Abashin
  20. Yeshaiahu Fainman
  21. Eliezer Masliah
  22. Srdjan Djurovic
  23. Ole Andreassen
  24. Gabriel A Silva
  25. David A Boas
  26. David Kleinfeld
  27. Richard B Buxton
  28. Gaute T Einevoll
  29. Anders M Dale
  30. Anna Devor  Is a corresponding author
  1. Faculty of Mechanical Engineering, Brno University of Technology and Institute of Physical Engineering, Czech Republic
  2. University of California, San Diego, United States
  3. Harvard Medical School, United States
  4. Norwegian University of Life Sciences, Norway
  5. Oslo University Hospital, Norway
  6. University of Oslo, Norway

Abstract

Identification of the cellular players and molecular messengers that communicate neuronal activity to the vasculature driving cerebral hemodynamics is important for (1) the basic understanding of cerebrovascular regulation and (2) interpretation of functional Magnetic Resonance Imaging (fMRI) signals. Using a combination of optogenetic stimulation and 2-photon imaging in mice, we demonstrate that selective activation of cortical excitation and inhibition elicits distinct vascular responses and identify the vasoconstrictive mechanism as Neuropeptide Y (NPY) acting on Y1 receptors. The latter implies that task-related negative Blood Oxygenation Level Dependent (BOLD) fMRI signals in the cerebral cortex under normal physiological conditions may be mainly driven by the NPY-positive inhibitory neurons. Further, the NPY-Y1 pathway may offer a potential therapeutic target in cerebrovascular disease.

Article and author information

Author details

  1. Hana Uhlirova

    CEITEC - Central European Institute of Technology, Faculty of Mechanical Engineering, Brno University of Technology and Institute of Physical Engineering, Brno, Czech Republic
    Competing interests
    No competing interests declared.
  2. Kıvılcım Kılıç

    Department of Neurosciences, University of California, San Diego, San Diego, United States
    Competing interests
    No competing interests declared.
  3. Peifang Tian

    Department of Neurosciences, University of California, San Diego, San Diego, United States
    Competing interests
    No competing interests declared.
  4. Martin Thunemann

    Department of Radiology, University of California, San Diego, San Diego, United States
    Competing interests
    No competing interests declared.
  5. Michele Desjardins

    Department of Radiology, University of California, San Diego, San Diego, United States
    Competing interests
    No competing interests declared.
  6. Payam A Saisan

    Department of Neurosciences, University of California, San Diego, San Diego, United States
    Competing interests
    No competing interests declared.
  7. Sava Sakadžić

    Martinos Center for Biomedical Imaging, Harvard Medical School, Charlestown, United States
    Competing interests
    No competing interests declared.
  8. Torbjørn V Ness

    Department of Mathematical Sciences and Technology, Norwegian University of Life Sciences, Ås, Norway
    Competing interests
    No competing interests declared.
  9. Celine Mateo

    Department of Physics, University of California, San Diego, San Diego, United States
    Competing interests
    No competing interests declared.
  10. Qun Cheng

    Department of Neurosciences, University of California, San Diego, San Diego, United States
    Competing interests
    No competing interests declared.
  11. Kimberly L Weldy

    Department of Neurosciences, University of California, San Diego, San Diego, United States
    Competing interests
    No competing interests declared.
  12. Florence Razoux

    Department of Neurosciences, University of California, San Diego, San Diego, United States
    Competing interests
    No competing interests declared.
  13. Matthieu Vanderberghe

    Department of Radiology, University of California, San Diego, San Diego, United States
    Competing interests
    No competing interests declared.
  14. Jonathan A Cremonesi

    Biology Undergraduate Program, University of California, San Diego, San Diego, United States
    Competing interests
    No competing interests declared.
  15. Christopher GL Ferri

    Department of Neurosciences, University of California, San Diego, San Diego, United States
    Competing interests
    No competing interests declared.
  16. Krystal Nizar

    Neurosciences Graduate Program, University of California, San Diego, San Diego, United States
    Competing interests
    No competing interests declared.
  17. Vishnu B Sridhar

    Department of Bioengineering, University of California, San Diego, San Diego, United States
    Competing interests
    No competing interests declared.
  18. Tyler C Steed

    Neurosciences Graduate Program, University of California, San Diego, San Diego, United States
    Competing interests
    No competing interests declared.
  19. Maxim Abashin

    Department of Electrical and Computer Engineering, University of California, San Diego, San Diego, United States
    Competing interests
    No competing interests declared.
  20. Yeshaiahu Fainman

    Department of Electrical and Computer Engineering, University of California, San Diego, San Diego, United States
    Competing interests
    No competing interests declared.
  21. Eliezer Masliah

    Department of Neurosciences, University of California, San Diego, San Diego, United States
    Competing interests
    No competing interests declared.
  22. Srdjan Djurovic

    Department of Medical Genetics, Oslo University Hospital, Oslo, Norway
    Competing interests
    No competing interests declared.
  23. Ole Andreassen

    KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital, University of Oslo, Oslo, Norway
    Competing interests
    No competing interests declared.
  24. Gabriel A Silva

    Department of Bioengineering, University of California, San Diego, San Diego, United States
    Competing interests
    No competing interests declared.
  25. David A Boas

    Martinos Center for Biomedical Imaging, Harvard Medical School, Charlestown, United States
    Competing interests
    No competing interests declared.
  26. David Kleinfeld

    Department of Physics, University of California, San Diego, San Diego, United States
    Competing interests
    David Kleinfeld, Reviewing editor, eLife.
  27. Richard B Buxton

    Department of Radiology, University of California, San Diego, San Diego, United States
    Competing interests
    No competing interests declared.
  28. Gaute T Einevoll

    Department of Mathematical Sciences and Technology, Norwegian University of Life Sciences, Ås, Norway
    Competing interests
    No competing interests declared.
  29. Anders M Dale

    Department of Radiology, University of California, San Diego, San Diego, United States
    Competing interests
    No competing interests declared.
  30. Anna Devor

    Department of Radiology, University of California, San Diego, San Diego, United States
    For correspondence
    adevor@ucsd.edu
    Competing interests
    No competing interests declared.

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols (#S07360, S14275) of the University of California San Diego.

Reviewing Editor

  1. Sacha B Nelson, Brandeis University, United States

Publication history

  1. Received: January 9, 2016
  2. Accepted: May 30, 2016
  3. Accepted Manuscript published: May 31, 2016 (version 1)
  4. Version of Record published: July 5, 2016 (version 2)

Copyright

© 2016, Uhlirova et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Hana Uhlirova
  2. Kıvılcım Kılıç
  3. Peifang Tian
  4. Martin Thunemann
  5. Michele Desjardins
  6. Payam A Saisan
  7. Sava Sakadžić
  8. Torbjørn V Ness
  9. Celine Mateo
  10. Qun Cheng
  11. Kimberly L Weldy
  12. Florence Razoux
  13. Matthieu Vanderberghe
  14. Jonathan A Cremonesi
  15. Christopher GL Ferri
  16. Krystal Nizar
  17. Vishnu B Sridhar
  18. Tyler C Steed
  19. Maxim Abashin
  20. Yeshaiahu Fainman
  21. Eliezer Masliah
  22. Srdjan Djurovic
  23. Ole Andreassen
  24. Gabriel A Silva
  25. David A Boas
  26. David Kleinfeld
  27. Richard B Buxton
  28. Gaute T Einevoll
  29. Anders M Dale
  30. Anna Devor
(2016)
Cell type specificity of neurovascular coupling in cerebral cortex
eLife 5:e14315.
https://doi.org/10.7554/eLife.14315

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