Cell type specificity of neurovascular coupling in cerebral cortex

Elife. 2016 May 31;5:e14315. doi: 10.7554/eLife.14315.


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.

Keywords: 2-photon microscopy; NPY; constriction; dilation; mouse; neuroscience; optogenetic.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cerebral Cortex / blood supply
  • Cerebral Cortex / drug effects*
  • Cerebral Cortex / metabolism
  • Cerebral Cortex / physiopathology
  • Cerebrovascular Disorders / drug therapy
  • Cerebrovascular Disorders / genetics
  • Cerebrovascular Disorders / metabolism
  • Cerebrovascular Disorders / physiopathology
  • Diagnostic Imaging
  • Gene Expression
  • Magnetic Resonance Imaging
  • Male
  • Mice
  • Mice, Transgenic
  • Neurons / cytology
  • Neurons / drug effects
  • Neurons / metabolism
  • Neuropeptide Y / pharmacology*
  • Neurovascular Coupling / drug effects*
  • Optogenetics
  • Organ Specificity
  • Oxygen / metabolism
  • Photic Stimulation
  • Protein Binding
  • Receptors, Neuropeptide Y / genetics
  • Receptors, Neuropeptide Y / metabolism*
  • Vasoconstriction / drug effects
  • Vasoconstrictor Agents / pharmacology*


  • Neuropeptide Y
  • Receptors, Neuropeptide Y
  • Vasoconstrictor Agents
  • Oxygen