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
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Research Support, Non-U.S. Gov't
MeSH terms
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Afferent Pathways / physiology
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Animals
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Animals, Newborn
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Astrocytes / cytology
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Astrocytes / drug effects
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Astrocytes / metabolism*
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Brain / blood supply*
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Brain / cytology
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Brain / metabolism
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Calcium Signaling / drug effects
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Calcium Signaling / physiology
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Cell Communication / drug effects
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Cell Communication / physiology*
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Cerebral Cortex / blood supply
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Cerebral Cortex / cytology
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Cerebral Cortex / metabolism
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Cerebrovascular Circulation / physiology*
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Electric Stimulation
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Enzyme Inhibitors / pharmacology
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Excitatory Amino Acid Antagonists / pharmacology
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Glutamic Acid / metabolism
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Microcirculation / cytology
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Microcirculation / drug effects
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Microcirculation / metabolism*
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Neurons / cytology
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Neurons / drug effects
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Neurons / metabolism*
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Nitric Oxide / metabolism
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Rats
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Rats, Wistar
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Receptors, Metabotropic Glutamate / antagonists & inhibitors
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Receptors, Metabotropic Glutamate / metabolism
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Signal Transduction / drug effects
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Signal Transduction / physiology
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Vasodilation / drug effects
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Vasodilation / physiology*
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Vasodilator Agents / pharmacology
Substances
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Enzyme Inhibitors
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Excitatory Amino Acid Antagonists
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Receptors, Metabotropic Glutamate
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Vasodilator Agents
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Nitric Oxide
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Glutamic Acid