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

By Micaela Zonta, M. C. Angulo, S. Gobbo, B. Rosengarten, K. Hossmann, T. Pozzan, Giorgio Carmignoto. Nature Neuroscience, 2003

1,491 citations recorded by the source corpus.

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 [Ca2+]i oscillations in astrocytes. Inhibition of these Ca2+ 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 [Ca2+]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.

Subfields: Cellular and Molecular Neuroscience, Neurology

View Paper: https://www.semanticscholar.org/paper/2951e610a6f2dff077b9fa907cefe55e947c25b9

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Citations in the corpus

Astrocyte reactivity and reactive astrogliosis: costs and benefits. (2014, background): “Astrocytes were shown to control formation, maintenance, function, and removal of neuronal synapses (45, 68, 168, 228, 237, 238); help to control blood flow (104, 120, 153, 207, 276); and together with pericytes regulate the bloodbrain barrier (1, 11, 17, 133).”
An astrocytic basis of epilepsy (2005, background): “The preferential loading of fluorescent acetoxymethyl ester indicators by astrocytes has been extensively reporte”
Neuroinflammation and depression: A review (2020, background): “This vasodilatation effect was shown to be mediated by glutamate (Zonta et al., 2003), although there is less evidence regarding how vascular arteriolar dynamics affect glial and neural functioning.”
Glial Cells Dilate and Constrict Blood Vessels: A Mechanism of Neurovascular Coupling (2006, background): “In recent years, it has been suggested that glial cells contribute to neurovascular coupling in the brain (Paulson and Newman, 1987; Harder et al., 1998; Zonta et al., 2003; Filosa et al., 2004; Mulligan and MacVicar, 2004; Koehler et al., 2006).”
Sildenafil: from angina to erectile dysfunction to pulmonary hypertension and beyond (2006, background): “Static flow-measures might, however, not be the appropriate parameter to characterize changes in microcirculatory adaptation to demand, where this regulation is mediated via neurovascular coupling in a fast and fine-tuned manner [179] [180] [181] .”
Human brain mapping: hemodynamic response and electrophysiology. (2008, background): “Zonta et al. (2003) showed in rat cortical slices that the dilation of arterioles triggered by neuronal activity is dependent on glutamatemediated Ca2+ oscillations in astrocytes.”
Astrocytic Ca2+ signaling evoked by sensory stimulation in vivo (2006, background): “Furthermore, activation of astrocytic Ca 2+ signaling has often required excessive stimulation, including high-intensity electrical pulse”
The blood-brain barrier: an engineering perspective (2013, background): “…cells binds with the corresponding Frontiers in Neuroengineering www.frontiersin.org August 2013 | Volume 6 | Article 7 | 5 receptor (PDGFR-B) on pericytes, regulating recruitment of pericytes as well as their proliferation (Bell et al., 2010; Dalkara et al., 2011; Winkler et al., 2011).”
Astrocyte control of synaptic transmission and neurovascular coupling. (2006, background): “Although various aspects remain to be elucidated, most recent studies highlight a central role of neuron-to-astrocyte signaling in the local control of microcirculation (6, 60, 123, 145, 241, 242).”
Astrocyte-mediated control of cerebral blood flow (2006, background): “The fact that MAFP potently inhibited astrocyte-induced vasodilation suggested that arachidonic acid derivatives, produced by astrocytes in response to Ca 2+ increases, could be the messengers that modulated vascular ton”