Neuron-to-astrocyte signaling is central to the dynamic control of brain microcirculation

Nat Neurosci. 2003 Jan;6(1):43-50. doi: 10.1038/nn980.

Abstract

The cellular mechanisms underlying functional hyperemia--the coupling of neuronal activation to cerebral blood vessel responses--are not yet known. Here we show in rat cortical slices that the dilation of arterioles triggered by neuronal activity is dependent on glutamate-mediated [Ca(2+)](i) oscillations in astrocytes. Inhibition of these Ca(2+) responses resulted in the impairment of activity-dependent vasodilation, whereas selective activation--by patch pipette--of single astrocytes that were in contact with arterioles triggered vessel relaxation. We also found that a cyclooxygenase product is centrally involved in this astrocyte-mediated control of arterioles. In vivo blockade of glutamate-mediated [Ca(2+)](i) elevations in astrocytes reduced the blood flow increase in the somatosensory cortex during contralateral forepaw stimulation. Taken together, our findings show that neuron-to-astrocyte signaling is a key mechanism in functional hyperemia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Afferent Pathways / physiology
  • Animals
  • Animals, Newborn
  • Astrocytes / cytology
  • Astrocytes / drug effects
  • Astrocytes / metabolism*
  • Brain / blood supply*
  • Brain / cytology
  • Brain / metabolism
  • Calcium Signaling / drug effects
  • Calcium Signaling / physiology
  • Cell Communication / drug effects
  • Cell Communication / physiology*
  • Cerebral Cortex / blood supply
  • Cerebral Cortex / cytology
  • Cerebral Cortex / metabolism
  • Cerebrovascular Circulation / physiology*
  • Electric Stimulation
  • Enzyme Inhibitors / pharmacology
  • Excitatory Amino Acid Antagonists / pharmacology
  • Glutamic Acid / metabolism
  • Microcirculation / cytology
  • Microcirculation / drug effects
  • Microcirculation / metabolism*
  • Neurons / cytology
  • Neurons / drug effects
  • Neurons / metabolism*
  • Nitric Oxide / metabolism
  • Rats
  • Rats, Wistar
  • Receptors, Metabotropic Glutamate / antagonists & inhibitors
  • Receptors, Metabotropic Glutamate / metabolism
  • Signal Transduction / drug effects
  • Signal Transduction / physiology
  • Vasodilation / drug effects
  • Vasodilation / physiology*
  • Vasodilator Agents / pharmacology

Substances

  • Enzyme Inhibitors
  • Excitatory Amino Acid Antagonists
  • Receptors, Metabotropic Glutamate
  • Vasodilator Agents
  • Nitric Oxide
  • Glutamic Acid

Grant support