Astrocytes are the most abundant type of brain glial cells. Accumulating evidence indicates that the their role in the central nervous system is by no means limited to just providing structural and metabolic support to neurons as was thought previously. Astrocytes are closely associated with cerebral blood vessels – all penetrating and intracerebral arterioles and capillaries are enwrapped by astrocytic endfeet. Astrocytes regulate cerebrovascular tone controlling local blood supply to support metabolic demands of the brain areas with increased activity. However, direct evidence demonstrating the functional role of astrocytes in complex behaviors is limited. By having contacts with cerebral vasculature as well as multiple neurons, astrocytes are in a position to quickly relay blood-borne stimuli to modify the activity of neuronal networks. Does it reflect their functional importance for the function of brain interoceptors, which monitor key homeostatic parameters including glucose concentration, pH and PCO2 levels? Here we address this question by testing the hypothesis that astrocytes which reside within the respiratory and sympathatic chemosensitive areas of the brainstem are able to sense changes in pH and impart these changes on the activities of respiratory and sympathetic networks. We found, that astrocytes which reside within the “classical” brainstem chemoreceptor areas located near the ventral surface of the medulla oblongata are highly chemosensitive. They respond to small physiological decreases in pH with vigorous elevations in intracellular Ca2+ and vesicular release of ATP. ATP spreads astrocytic Ca2+ excitation, activates key chemoreceptor neurons and induces adaptive increases in breathing. Mimicking pH-evoked Ca2+ responses by selective light stimulation of astrocytes expressing channelrhodopsin-2 activates chemoreceptor neurons via ATP-dependent mechanism and triggers robust respiratory and sympathetic responses in vivo. Thus, medullary astrocytes have the unique ability to sense small changes in PCO2/[H+] and then impart these changes into a modified pattern of cardiorespiratory activity. This identifies astroglia as an important component of one of the most fundamental mammalian homeostatic reflexes and provides strong direct evidence for an active role of astrocytes in the information processing in the central nervous system.
University of Manchester (2010) Proc Physiol Soc 19, SA10
Research Symposium: Role of astrocytes in respiratory-sympathetic coupling
A. Gourine1, S. Kasparov2
1. University College London, London, United Kingdom. 2. University of Bristol, Bristol, United Kingdom.
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Where applicable, experiments conform with Society ethical requirements.