Astrocytes Control Breathing Through pH-dependent Release of ATP

By A. Gourine, V. Kasymov, N. Marina, F. Tang, M. Figueiredo, S. Lane, A. Teschemacher, K. Spyer, Karl Deisseroth, S. Kasparov. Science, 2010

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Astrocytes, ATP, Brainstem, and Breathing Astrocytes (or glial cells), previously assumed to be passive players in brain physiology, may play a functional role in a number of complex behaviors. The central chemosensory control of breathing involves highly specialized neuronal populations in the brainstem, but what about astrocytes? Gourine et al. (p. 571, published online 15 July) now present evidence that glial cells may help to control breathing. A number of techniques were used to reveal glial calcium rises in vitro that elicit a depolarization of neurons in the primary locus for central respiratory chemosensitivity. The depolarization in these neurons is evoked by vesicular release of ATP in neighboring astrocytes in response to the fall in extracellular pH. Thus, brainstem astrocytes have the ability to sense changes in blood and brain CO2, and pH directly, and may control the activity of the respiratory neuronal networks to regulate breathing. Central nervous system glial cells are key players in the chemo-reflex essential for breathing. Astrocytes provide structural and metabolic support for neuronal networks, but direct evidence demonstrating their active role in complex behaviors is limited. Central respiratory chemosensitivity is an essential mechanism that, via regulation of breathing, maintains constant levels of blood and brain pH and partial pressure of CO2. We found that astrocytes of the brainstem chemoreceptor areas are highly chemosensitive. They responded to physiological decreases in pH with vigorous elevations in intracellular Ca2+ and release of adenosine triphosphate (ATP). ATP propagated astrocytic Ca2+ excitation, activated chemoreceptor neurons, and induced adaptive increases in breathing. Mimicking pH-evoked Ca2+ responses by means of optogenetic stimulation of astrocytes expressing channelrhodopsin-2 activated chemoreceptor neurons via an ATP-dependent mechanism and triggered robust respiratory responses in vivo. This demonstrates a potentially crucial role for brain glial cells in mediating a fundamental physiological reflex.

Subfields: Cellular and Molecular Neuroscience, Cognitive Neuroscience, Endocrine and Autonomic Systems

View Paper: https://www.semanticscholar.org/paper/a82f120c7c280f8b91841b9e592a950787f3fd06

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Citations in the corpus

Astrocytes are endogenous regulators of basal transmission at central synapses. (2011, neutral): “Integrated Presynaptic and Glial Mechanisms The regulatory role of astrocytes in basal synaptic transmission may be relevant to many other types of synapses in the CNS because they regulate synaptic transmission and plasticity in numerous brain areas (Gordon et al., 2009; Gourine et al., 2010; Matsu”
Physiology of Astroglia. (2018, neutral): “In the brain stem, astroglia-derived ATP signals to respiratory neuronal network, thus initiating ventilatory response (598, 1875).”
The Development and Application of Optogenetics (2011, background): “Viruses have been used to target (among other cells) hypocretin neurons (Adamantidis et al. 2007), excitatory pyramidal neurons (Lee et al. 2010, Sohal et al. 2009, Zhang et al. 2007a), and astroglia (Gourine et al. 2010, Gradinaru et al. 2009).”
Gliotransmitters Travel in Time and Space (2014, background): “Similarly, astrocytes can exchange information concerning immune state with microglia and detect local pH and osmolality changes to control breathing (Gourine et al., 2010) and water homeostasis, respectively (Haj-Yasein et al.”