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Eric Newman"Conversations Between Glia, Neurons and Blood Vessels in the Retina"

Abstract :


Neuronal activity in the central nervous system elicits localized changes in blood flow, a response termed functional hyperemia.
The cellular mechanisms that underlie functional hyperemia, however, are not well understood. We have investigated the role of glial cells in mediating functional hyperemia using an ex vivo preparation of the isolated rodent retina.
We investigated whether neuronal activity stimulates glial cells in the retina. We found that flickering light, which activates retinal neurons, also evokes Ca2+ increases in Müller cells, the principal glial cells of the retina. Light-evoked glial Ca2+ increases are blocked by purinergic antagonists, demonstrating that neuron to glia signaling is mediated by neuronal release of ATP.
We have also investigated two proposed mechanisms of glial control of the vasculature: glial K+ siphoning and glial induction of vasoactive arachidonic acid metabolites. In K+ siphoning, current flowing through glial cells transfers K+ released from active neurons to blood vessels. Our results suggest that glial K+ siphoning does not contribute significantly to neurovascular coupling in the retina.
Instead, our experiments indicate that glial cells mediate neurovascular coupling by inducing the production of two types of arachidonic acid metabolites, EETs and 20-HETE, which dilate and constrict vessels, respectively. We show that both light flashes and direct glial stimulation produce vasodilation or vasoconstriction mediated by EETs and 20-HETE. The type of vasomotor response observed (dilation or constriction) depends on retinal levels of nitric oxide and oxygen. Our data also demonstrate that glial cells are necessary intermediaries for signaling from neurons to blood vessels, as functional hyperemia does not occur when neuron to glia communication is interrupted. These results indicate that glial cells play an important role in mediating functional hyperemia and suggest that the regulation of blood flow may involve both vasodilating and vasoconstricting components.   

Selected publications

Metea, M.R., Newman, E.A. (2007) Signaling within the neurovascular unit in the retina. Exp. Physiol. 92.4:635-640.
Metea, M.R., Kofuji, P., Newman, E.A. (2007) Neurovascular coupling is not mediated by potassium siphoning from glial cells. J. Neurosci. 27:2468-2471.
Metea, M.R. and Newman, E.A. (2006) Glial cells dilate and constrict blood vessels: A mechanism of neurovascular coupling. J. Neurosci., 26:2862-2870. PDF

Stéphane Oliet