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.

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.

Metrics

  • 6,169
    views
  • 1,468
    downloads
  • 162
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  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

Share this article

https://doi.org/10.7554/eLife.14315

Further reading

    1. Developmental Biology
    2. Neuroscience
    Changtian Ye, Ryan Ho ... James Q Zheng
    Research Article

    Environmental insults, including mild head trauma, significantly increase the risk of neurodegeneration. However, it remains challenging to establish a causative connection between early-life exposure to mild head trauma and late-life emergence of neurodegenerative deficits, nor do we know how sex and age compound the outcome. Using a Drosophila model, we demonstrate that exposure to mild head trauma causes neurodegenerative conditions that emerge late in life and disproportionately affect females. Increasing age-at-injury further exacerbates this effect in a sexually dimorphic manner. We further identify sex peptide signaling as a key factor in female susceptibility to post-injury brain deficits. RNA sequencing highlights a reduction in innate immune defense transcripts specifically in mated females during late life. Our findings establish a causal relationship between early head trauma and late-life neurodegeneration, emphasizing sex differences in injury response and the impact of age-at-injury. Finally, our findings reveal that reproductive signaling adversely impacts female response to mild head insults and elevates vulnerability to late-life neurodegeneration.

    1. Neuroscience
    Iustin V Tabarean
    Research Article

    Neurotensin (Nts) is a neuropeptide acting as a neuromodulator in the brain. Pharmacological studies have identified Nts as a potent hypothermic agent. The medial preoptic area, a region that plays an important role in the control of thermoregulation, contains a high density of neurotensinergic neurons and Nts receptors. The conditions in which neurotensinergic neurons play a role in thermoregulation are not known. In this study, optogenetic stimulation of preoptic Nts neurons induced a small hyperthermia. In vitro, optogenetic stimulation of preoptic Nts neurons resulted in synaptic release of GABA and net inhibition of the preoptic pituitary adenylate cyclase-activating polypeptide (Adcyap1) neurons firing activity. GABA-A receptor antagonist or genetic deletion of Slc32a1 (VGAT) in Nts neurons unmasked also an excitatory effect that was blocked by a Nts receptor 1 antagonist. Stimulation of preoptic Nts neurons lacking Slc32a1 resulted in excitation of Adcyap1 neurons and hypothermia. Mice lacking Slc32a1 expression in Nts neurons presented changes in the fever response and in the responses to heat or cold exposure as well as an altered circadian rhythm of body temperature. Chemogenetic activation of all Nts neurons in the brain induced a 4–5°C hypothermia, which could be blocked by Nts receptor antagonists in the preoptic area. Chemogenetic activation of preoptic neurotensinergic projections resulted in robust excitation of preoptic Adcyap1 neurons. Taken together, our data demonstrate that endogenously released Nts can induce potent hypothermia and that excitation of preoptic Adcyap1 neurons is the cellular mechanism that triggers this response.