Neuron-to-astrocyte signaling is central to the dynamic control of brain microcirculation.
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.
Zonta
Micaela
M
Istituto CNR di Neuroscienze and Dipartimento di Scienze Biomediche Sperimentali, Università di Padova, viale G. Colombo 3, 35121 Padova, Italy.
Angulo
María Cecilia
MC
Gobbo
Sara
S
Rosengarten
Bernhard
B
Hossmann
Konstantin-A
KA
Pozzan
Tullio
T
Carmignoto
Giorgio
G
D000344:Afferent Pathways / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D001921:Brain / Q000098:blood supply* / Q000166:cytology / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D002450:Cell Communication / Q000187:drug effects / Q000502:physiology*; D002540:Cerebral Cortex / Q000098:blood supply / Q000166:cytology / Q000378:metabolism; D002560:Cerebrovascular Circulation / Q000502:physiology*; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism; D008833:Microcirculation / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
D004791:Enzyme Inhibitors; D018691:Excitatory Amino Acid Antagonists; D018094:Receptors, Metabotropic Glutamate; D014665:Vasodilator Agents; D009569:Nitric Oxide; D018698:Glutamic Acid