Vascular Compartmentalization of Functional Hyperemia from the Synapse to the Pia

Neuron. 2018 Jul 25;99(2):362-375.e4. doi: 10.1016/j.neuron.2018.06.012. Epub 2018 Jun 21.


Functional hyperemia, a regional increase of blood flow triggered by local neural activation, is used to map brain activity in health and disease. However, the spatial-temporal dynamics of functional hyperemia remain unclear. Two-photon imaging of the entire vascular arbor in NG2-creERT2;GCaMP6f mice shows that local synaptic activation, measured via oligodendrocyte precursor cell (OPC) Ca2+ signaling, generates a synchronous Ca2+ drop in pericytes and smooth muscle cells (SMCs) enwrapping all upstream vessels feeding the activated synapses. Surprisingly, the onset timing, direction, and amplitude of vessel diameter and blood velocity changes vary dramatically from juxta-synaptic capillaries back to the pial arteriole. These results establish a precise spatial-temporal sequence of vascular changes triggered by neural activity and essential for the interpretation of blood-flow-based imaging techniques such as BOLD-fMRI.

Keywords: CBF; anesthetized; astrocyte; awake; blood-brain barrier; calcium; endothelium; functional imaging; gap junction; glia; glutamate; hyperpolarization; in vivo; microvascular; neuron; neurovascular coupling; neurovascular unit; odor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / blood supply*
  • Brain / physiology*
  • Brain Chemistry / physiology
  • Hyperemia / diagnosis
  • Hyperemia / physiopathology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Microscopy, Confocal / methods
  • Muscle, Smooth, Vascular / chemistry
  • Muscle, Smooth, Vascular / physiology
  • Pericytes / chemistry
  • Pericytes / physiology
  • Pia Mater / blood supply*
  • Pia Mater / chemistry
  • Pia Mater / physiology*
  • Synapses / chemistry
  • Synapses / physiology*