Vasculo-neuronal coupling: Retrograde vascular communication to brain neurons

Ki Jung Kim, Juan Ramiro Diaz, Jennifer A. Iddings, Jessica A. Filosa

Research output: Contribution to journalArticlepeer-review

67 Scopus citations


Continuous cerebral blood flow is essential for neuronal survival, but whether vascular tone influences resting neuronal function is not known. Using a multidisciplinary approach in both rat and mice brain slices, we determined whether flow/pressure-evoked increases or decreases in parenchymal arteriole vascular tone, which result in arteriole constriction and dilation, respectively, altered resting cortical pyramidal neuron activity.Wepresent evidence for intercellular communication in the brain involving a flow of information from vessel to astrocyte to neuron, a direction opposite to that of classic neurovascular coupling and referred to here as vasculo-neuronal coupling (VNC). Flow/pressure increases within parenchymal arterioles increased vascular tone and simultaneously decreased resting pyramidal neuron firing activity. On the other hand, flow/pressure decreases evoke parenchymal arteriole dilation and increased resting pyramidal neuron firing activity. In GLAST-CreERT2; R26-lsl-GCaMP3 mice, we demonstrate that increased parenchymal arteriole tone significantly increased intracellular calcium in perivascular astrocyte processes, the onset of astrocyte calcium changes preceded the inhibition of cortical pyramidal neuronal firing activity. During increases in parenchymal arteriole tone, the pyramidal neuron response was unaffected by blockers of nitric oxide, GABAA, glutamate, or ecto-ATPase. However, VNC was abrogated by TRPV4 channel, GABAB, as well as an adenosine A1 receptor blocker. Differently to pyramidal neuron responses, increases in flow/pressure within parenchymal arterioles increased the firing activity of a subtype of interneuron. Together, these data suggest that VNC is a complex constitutive active process that enables neurons to efficiently adjust their resting activity according to brain perfusion levels, thus safeguarding cellular homeostasis by preventing mismatches between energy supply and demand.

Original languageEnglish (US)
Pages (from-to)12624-12639
Number of pages16
JournalJournal of Neuroscience
Issue number50
StatePublished - Dec 14 2016


  • Adenosine
  • Astrocytes
  • Calcium
  • Myogenic tone
  • Neurovascular coupling
  • TRPV4 channels

ASJC Scopus subject areas

  • Neuroscience(all)


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